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Clinical Neurology > MED629A - Applied Neuroanatomy > Flashcards

MED629A - Applied Neuroanatomy Flashcards

1
Q

Define Rostral and Caudal

A

Rostral - towards nose

Caudal - towards tail (posterior in brain)

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2
Q

Define Ventral and Dorsal

A

Ventral - anterior (inferior in cortex)

Dorsal - posterior (superior in cortex)

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3
Q

What are Brodmann areas?

A

Map of the grey matter of the brain according to the function

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4
Q

What are the functions of the frontal lobe?

A

Involved in higher intellectual function including emotions, mood, behaviour, planning ahead, prediction, and inhibition.

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5
Q

Where is the Broca’s are located?

A

Frontal lobe

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6
Q

What is the function of Broca’s area?

A

Motor articulation of speech

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7
Q

How is the pre-central gyrus organised?

A

Somatotopically and topographically

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8
Q

What does somatotopically organised mean?

A

Amount of brain tissue corresponds to how fine the movement of the body part is. The more muscle units require more nerves

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9
Q

What does topographically organised mean?

A

Differents areas of brain tissue correspond to different body parts. (Homunculus)

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10
Q

What are the functions of the Parietal lobe?

A

Spatial sense + navigation, integrating sensory info

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11
Q

What is the function of the post-central gyrus?

A

Sensation of pain, temp, touch and pressure. Conscious proprioception. It is somatotopically organised - the more area of tissue the more accurate the 2 point discrimination of a body part.

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12
Q

What do structural abnormalities in the ventral region of the parietal lobe result in?

A

Reading disabilities

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13
Q

What is the function of the posterior parietal lobe?

A

Logic of maths (abstract neural function)

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14
Q

What is the function of the occipital lobe?

A

Visual information
Somatotopically arranged
Damage results in partial or complete blindness

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15
Q

Where is Wernicke’s area located?

A

Temporal lobe

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16
Q

What are the functions of the different areas of the temporal lobe?

A

Dorsolateral - hearing
Ventromedial - memory processing
Anterior pole - complex memory and imaging processes
Wernicke’s area - sensory and speech - comprehension and formulation
Remaining area - integration of multiple sensory functions e.g. auditory + visual + touch

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17
Q

What is the function of the cerebellum?

A

Co-ordination of movement and balance

Cognitive functioning - parallel processing allows multitasking

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18
Q

What symptoms does damage to each area of the cerebellum result in?

A

Vermis - balance problems due to loss of postural control (difficulty sitting and standing)
Hemispheres - ipsilateral impaired limb coordination
Bilateral hemispheres - slowed/slurred speech (dysarthria), impaired coordination, both arms, wide based unsteady gait (cerebellar ataxia)

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19
Q

Where is the insula located?

A

It forms the floor of the lateral sulcus

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20
Q

What is the Operculum?

A

Latin for lips - it is the parts of the temporal, frontal and parietal lobes that overlie the insula

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21
Q

What separates the two hemispheres?

A

Deep longitudinal fissure

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22
Q

What is the Corpus callosum?

A

A large bundle of white matter connecting the two hemispheres

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23
Q

What are the three layers of the cranial meninges?

A

Dura mater
Arachnoid mater
Pia mater

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24
Q

What are the two layers of the dura mater?

A

The outer endosteal layer that lines the interior of the skull and the inner meningeal layer that envelopes the CNS

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25
Q

What are formed when the two layers of the dura separate to form dura folds?

A

Dural venous sinuses

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26
Q

Where is the falx cerebri?

A

Lies in the deep longitudinal fissure

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27
Q

What is the tentorium cerebelli?

A

Dura forming a fibrous roof over the posterior cranial fossa and the cerebellum

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28
Q

What separates the two layers of the cerebellum?

A

Falx cerebelli

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29
Q

What are the contents of the cavernous sinus and why is this important clinically?

A 
Oculomotor nerve
Trochlear nerve
Ophthalmic branch of the trigeminal nerve
Maxillary branch of the trigeminal nerve
Internal carotid artery
Abducens nerve
Trochlear nerve

Important clinically as you can get bleeds and thrombus here resulting in nerve palsies

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30
Q

What are subarachnoid cisterns and what are they full of?

A

Spaces that exist between the arachnoid and the pia where the arachnoid spans the gyri and they are full of CSF

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31
Q

What does the interpeduncular cistern contain?

A

The circle of willis

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32
Q

What is the pia mater?

A

Closely adherent to the underlying nervous tissue and is indistinguishable with the naked eye
It forms part of the blood brain barrier

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33
Q

What is the blood brain barrier formed of?

A

1) The endothelial cells of the capillaries
2) The basement membrane formed from the true basement membrane and the pia
3) The astrocytic end feet

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34
Q

What are the two vessels that supply the brain with blood and where do they arise?

A 
Internal carotid (80%) which arises at the bifurcation of the common carotid at the level of C4
Vertebral arteries (20%) which arise from the first part of the subclavian
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35
Q

What are the terminal branches of the internal carotid and what do they supply?

A

Ophthalmic artery - supplies structures of the orbit
Posterior communicating artery - acts as anastomotic connecting vessel in the circle of willis
Anterior choroidal artery - supplies parts of the brain that are important for motor control and vision
Anterior cerebral artery - supplies the corpus callosum and the medial aspects of the hemispheres

Continues on as the middle cerebral artery which supplies the majority of the lateral surfaces of the hemispheres and the deep structures of the anterior part of the cerebral hemispheres

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36
Q

What are the branches of the vertebral arteries and what do they supply?

A
  • Meningeal branch – supplies the falx cerebelli
  • Anterior and posterior spinal arteries – supplies the spinal cord, spanning its entire length
  • Posterior inferior cerebellar artery – supplies the cerebellum
  • Converge to form the basilar artery
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37
Q

What are the two types of cerebral veins?

A

Internal cerebral veins - within the brain tissue and end when they reach the surface of the brain

External cerebral veins - run on the surface of the brain, cross the subarachnoid space, drain into the dural venous sinuses

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38
Q

What are the function of emissary veins and why are they clinically important?

A

Allow communication between the venous sinuses and the veins outside skull. They can be a route of infection and inflammation into the skull

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39
Q

What is the function of the choroid plexus?

A

Responsible for the majority of CNS production

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40
Q

Where are the majority of the choroid plexus located?

A

The lateral ventricles

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41
Q

Describe the journey of CSF through the brain

A

1) CSF is produced in the lateral ventricles
2) Passes from the lateral ventricles into the 3rd ventricle via interventricular foramen (foramen of monro)
3) Passes into the 4th ventricle via the cerebral aqueduct
4) Enters the subarachnoid space via the foramen of magendie and the foramina of Luschka

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42
Q

Name the foramina in the IVth ventricle and their location

A

Foramen of Magendie - medial

Foramina of Luschka - lateral

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43
Q

What cells does the choroid plexus contain?

A

Ependymal cells

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44
Q

What stops the majority of substances entering the CSF (Blood-CSF barrier)

A

Tight junctions in the membranes facing the ventricles of the ependymal cells

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45
Q

What is the function of neurones?

A

Intercellular communication and electrical signalling via synapses

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46
Q

What do dendrites do?

A

Receive inputs via dendritic spines, transmit to cell bodies (soma)

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47
Q

What is an axon hillock?

A

Where action potentials propagate along axons from

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48
Q

When are neurons formed?

A

Mainly, but not exclusively, during brain development

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49
Q

What is H&E and what does it stain?

A

Haematoxylin and Eosin

Haematoxylin - stains nucleic acids blue
Eosin - stains proteins ed

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50
Q

What are Nissl substances?

A

Rough endoplasmic reticulum

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51
Q

What is LFB and what does it stain?

A

Luxol Fast Blue - stains myelin

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52
Q

What is CV and what does it stain?

A

Cresyl violet - stains Nissle (RER)

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53
Q

Where are synapses located?

A

Concentrated on dendritic spines

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54
Q

What are some examples of excitatory neurotransmitters?

A

Glutamate (most common neurotransmitter in CNS)
Acetylcholine
Adrenaline

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55
Q

What are the two types of synapses?

A

Chemical and Electrical

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56
Q

What is the most common type of synapse?

A

Chemical

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57
Q

How can you distinguish between the two types of synapse?

A

Using an electron microscope
Chemical - electron dense material only on post-synaptic side
Electrical - electron dense material on both sides of synapse

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58
Q

What do electrical synapses allow?

A

Synchronized electrical activity

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59
Q

Name two examples of where electrical synapses could be found?

A

Brainstem neurons - breathing

Hypothalamus - hormone secretion

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60
Q

What is plasticity?

A

Can become stronger or weaker

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61
Q

What is neural plasticity of the basis of?

A

Learning and memory

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62
Q

What is spine remodelling linked to?

A

Neural activity - the more activity the more dendrites

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63
Q

How are dendritic spines dynamic structures?

A

Can change quantity, size and composition

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64
Q

What is the neocortex?

A

Top layer of the cerebral hemispheres

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65
Q

How do neurons vary in the neocortex? (Neuronal heterogeneity)

A

Size, morphology, electrical properties, neurotransmitters

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66
Q

What are some of the properties of UMN?

A

Large, excitatory, glutamatergic, long projections, pyramidal

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67
Q

What are some of the properties of striatal interneurons?

A

Small, spiny, inhibitory, GABAergic

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68
Q

Name three types of differentiated glia

A

Oligodendrocytes
Microglia
Astrocytes

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69
Q

What are oligodendrocytes and what are their function?

A

Myelinating cells of the CNS that are unique to vertebrates.

Enables rapid nerve conduction and provides metabolic support for axons

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70
Q

What appearance do oligodendrocytes have in histology?

A

Fried egg appearance

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71
Q

What are nodes of ranvier and what do they allow?

A

Interruptions of the myelin sheath - allow saltatory conduction

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72
Q

What is the myelin sheath formed of?

A

Formed by wrapping of axons by oligodendrocyte processes

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73
Q

What is the myelin sheath made of?

A

70% lipid, 30% protein

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74
Q

Name some myelin specific proteins

A

MBP, MAG, MOG, PLP, PMP22

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75
Q

What is the function of myelin specific proteins?

A

MSPs are positively charged compared to the negatively charged biological membranes
Allows the highly compaction of the myelin sheath
Are excellent markers

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76
Q

What are microglia?

A

Resident immune cells of the CNS

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77
Q

What are microglia derived from?

A

Erythromyeloid progenitors that migrate into CNS

Completely different embryological derivation than other glia

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78
Q

What is the resting state of microglia?

A

Highly ramified, motile processes, survey environment

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79
Q

What happens upon activation (e.g. by ATP) to microglia?

A

Retract processes, become amoeboid and motile

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80
Q

What are the functions of microglia?

A
  • Proliferate at sites of injury
  • Immune surveillance
  • Phagocytosis - debris/microbes
  • Synaptic plasticity - pruning (removing synapses)
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81
Q

What are astrocytes?

A

Star like cells, most numerous glial cell in the CNS.

Highly heterogenous - not all star-shaped

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82
Q

What is the common marker of astrocytes?

A

Glial fibrillary acidic protein (GFAP)

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83
Q

What are the two types of astrocytes?

A

Fibrous - white matter, less elaborate, contact blood vessels, pial surface and nodes of ranvier

Protoplasmic - grey matter, extremely elaborate, processes contact blood vessels and pial surface

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84
Q

What are the functions of astrocytes?

A

o Developmental – radial glia – neuro stem cells
o Structural – define brain micro-architecture
o Envelope synapses – tripartite synapse
o Homeostatic – buffer K+, glutamate etc
o Support neurons – Glutamate-glutamine shuttle, lactate shuttle, etc
o Neurovascular coupling (basis of fMRI) – increased neural activity leads to increased blood flow
o Disease relevance – gliosis, astrocytosis (due to destruction of nearby neurones)

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85
Q

Name three specialised astrocytes and where they can be found

A

o Radial glia (cortex)
o Bergmann glia (cerebellum) – support purkinje fibres
o Muller cells (retina)

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86
Q

What is nuclei?

A

Abundance of neuronal cell bodies in nuclei

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87
Q

What are tracts?

A

Axons in the CNS gather to form tracts

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88
Q

What are tracts that cross midline called?

A

Commissures

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89
Q

What is neuropil?

A

Grey matter that contains an abundance of processes but few cell bodies

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90
Q

What do axons bundle to form in the PNS?

A

Nerves

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91
Q

What are Schwann cells?

A

Myelinating cells of the PNS, they have a different developmental origin than oligodendrocytes

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92
Q

Where are cell bodies and supporting cells located in the PNS?

A

Located in the ganglia

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93
Q

How was the blood brain barrier discovered?

A

From injection of dyes into blood and CSF.

Dyes did not cross into CSF when injected into blood and vice versa

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94
Q

What is the blood brain barrier sensitive to?

A

Inflammation, hypertension, trauma and ischaemia

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95
Q

What is the blood brain barrier a problem for?

A

Drug delivery

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96
Q

What lacks a normal blood brain barrier and why?

A

Circumventricular organs - involved in homeostatic regulation and hormone release (pineal and pituitary gland) so need reduced BBB

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97
Q

What is radiculopathy?

A

Pathology of the nerve root e.g. sciatica

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98
Q

What are some UMN signs?

A

o Spasticity
o Pyramidal pattern weakness
o Brisk reflexes with clonus and extensor plantars (loss of inhibition)

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99
Q

Name some examples of UMN lesions

A

Stroke, MS, brain tumours, encephalitis, motor neurone disease

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100
Q

What are some LMN signs?

A

o Flaccidity, wasting and fasciculations
o Distal weakness
o Absent reflexes, plantars flexor or mute

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101
Q

Name some examples of LMN lesions

A

diabetic neuropathy, lumbar nerve root compression, polio, motor neuron disease

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102
Q

What are the two different types of tone and what do they signify?

A

Spasticity - like a clasp knife - pyramidal tracts (e.g. stroke)

Rigidity - like a lead pipe - basal ganglia (extrapyramidal) system (e.g. parkinson’s)

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103
Q

What is the role of the basal ganglia?

A

Involved in the initiation and control of movement

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104
Q

Name the regions that make up the basal ganglia

A

Caudate nucleus, putamen and globus pallidus, subthalamic nucleus, substantia nigra

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105
Q

Briefly describe Brown-Sequard syndrome

A

Right lesion

  • Right sided weakness due to descending tract crossing over in medulla
  • Left sided loss of pain and temperature sensation– spinothalamic tract crosses shortly after entering spinal cord
  • Right sided loss of proprioception, fine touch and vibration - dorsal column deccussates in medulla
  • Localized right sided loss of pain and temperature at level of lesion as tracts do not decussate immediately
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106
Q

What are the clinical features of cerebellar disease?

A 
DANISH
Dysdiadochokinesia
Ataxia
Nystagmus
Intention tremor
Slurred speech
Hypotonia
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107
Q

What does the eye look like in a third nerve palsy?

A

Globe depressed and abducted, sometimes with a fixed dilated pupil

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108
Q

Describe the difference between surgical and medical IIIrd nerve palsy

A

o Medical – Pupil sparing – can be due to microvascular damage of nerve (e.g. due to diabetes)
o Surgical - pupil fixed and dilated
o Parasympathetic nerve fibres are situated on the outside of the nerve
o Compression of the nerve (e.g. by tumour or aneurysm) results in parasympathetic dysfunction – pupil fixed and dilated
o More worried about surgical – CT scan

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109
Q

What is internuclear ophthalmoplegia and what can it be a sign of?

A
  • Lesion of medial longitudinal fasciculus – interneuron that connects 3RD and 6th cranial nerves
  • Allows the eyes to move together – lateral rectus in one eye contracting simultaneously with medial rectus in the other
  • Results in asymmetry nystagmus – nystagmus in eye that is fine – and slow movement of one eye compared to the other
  • Almost diagnostic of multiple sclerosis – in young people
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110
Q

What is Horner’s syndrome and what are the clinical signs?

A
  • Due to damage of the sympathetic nerves of the face
  • Miosis – contraction of the pupil
  • Ptosis – drooping of the upper eyelid
  • Anhidrosis – absence of sweating to the face
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111
Q

What is lateral medullary syndrome and what are the clinical features?

A
  • Caused by ischaemia in the lateral part of the medulla in
Ipsilateral side
o	Horner’s syndrome
o	Limb ataxia
o	Loss of facial sensation of pain and temperature on the face, reduced corneal reflex
o	Dysarthria and dysphagia

Contralateral side
o Loss of pain and temperature sensation

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112
Q

What are some causes of Brown Sequard syndrome?

A

o Inter Vertebral disc (IVD) prolapse
o Infection – HIV, Sjogren’s, HTLV1, ADEM
o Arterio Venous dural fistula
o MS

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113
Q

Name the bones of the skull

A
  • Frontal
  • Temporal
  • Parietal
  • Occipital
  • Sphenoid
  • Ethmoid
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114
Q

What are the three cranial fossae and what do they contain?

A 
Anterior cranial fossa – contains the 
o	frontal lobe of the brain 
o	Cribriform plate
o	Crista galli – falx cerebri attaches here 
o	Lesser wing of the sphenoid bone

Middle cranial fossa – contains the
o temporal, parietal and occipital lobes of the brain and is much deeper than the anterior cranial fossa
o Sphenoid bone – greater wings and body
o Pituitary (hypophyseal) fossa – part of the Sella turcica (where the pituitary gland sits)

Posterior cranial fossa – contains the cerebellum, pons and medulla and is the deepest

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115
Q

Name the important foramina of the skull

A 
Cribriform plate 
Optic canal
Superior orbital fissure
Foramen Rotundum
Foramen oval
Foramen Spinosum
Internal Acoustic Meatus
Jugular foramen
Hypoglossal canal
Foramen Magnum
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116
Q

What are the contents of the Cribriform plate?

A

Olfactory Nerve (CNI)

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117
Q

What are the contents of the Optic canal?

A

Optic nerve (CNII)

Ophthalmic artery

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118
Q

What are the contents of the Superior orbital fissure?

A

Oculomotor nerve (CNIII)

Trochlear nerve (CNIV)

Abducens nerve (CNVI)

Ophthalmic division of the trigeminal (CNV(1))

Superior ophthalmic vein

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119
Q

What are the contents of the Foramen Ovale?

A

Mandibular branch of the trigeminal (CNV(3))

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120
Q

What are the contents of the Foramen Spinosum?

A

Middle meningeal artery

Middle meningeal vein

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121
Q

What are the contents of the Internal Acoustic Meatus?

A

Facial nerve (CNVII)

Vestibulocochlear nerve (CNVIII)

Labyrinthine artery

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122
Q

What are the contents of the Jugular Foramen?

A

Glossopharyngeal nerve (CNIX)

Vagus nerve (CNX)

Accessory nerve (CNXI)

Internal jugular vein

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123
Q

What are the contents of the Hypoglossal Canal?

A

Hypoglossal nerve (CNXII)

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124
Q

What are the contents of the Foramen Magnum?

A

Spinal cord

Vertebral arteries

Anterior and posterior spinal arteries

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125
Q

What are the contents of the Foramen Rotundum?

A

Maxillary branch of the trigeminal (CNV(2))

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126
Q

Name the parts of a vertebra

A

o Vertebral body – weight bearing
o Pedicle – connect the body to the transverse processes
o Lamina – connect the spinous and the transverse processes
o Spinous process
o Transverse processes
o Superior and inferior articular processes

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127
Q

What are C1 and C2 called?

A

C1 - Atlas

C2 - Axis

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128
Q

Describe the distinguishing features of cervical vertebrae

A 
-	Bifid spinous processes 
o	C1 – no spinous process
o	C7 – longer and may not bifurcate 
-	Transverse foramina – an opening in each transverse process in which the vertebral arteries run in 
-	Triangular vertebral foramen
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129
Q

Describe the distinguishing features of thoracic vertebrae

A
  • Demi facets – superiorly and inferiorly placed on either side of the vertebral body.
  • Costal facet – on the transverse process
  • Spinous processes are oriented obliquely inferiorly and posteriorly
  • Vertebral foramen is circular
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130
Q

Describe the distinguishing features of the lumbar vertebra

A
  • Largest in the vertebral column
  • Very large kidney-shaped vertebral bodies – weight bearing
  • Lack transverse foramina, costal facets, bifid spinous processes
  • Triangular vertebral foramen
  • Spinous processes are shorter and do not extend inferiorly below the vertebral body
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131
Q

What are the curvatures of the spine?

A

Cervical and lumbar - lordosis

Thoracic - kyphosis

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132
Q

What are the two regions of an intervertebral disc?

A

Central nucleus pulposus surrounded by Annulus fibrosus

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133
Q

What is the Nucleus Pulposus and what does it contain?

A

well hydrated gel containing proteoglycan, collagen and cartilage cells

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134
Q

What is the Annulus Fibrosus?

A

10-12 concentric layers of collagen whose oblique arrangement alters in successive layers

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135
Q

Name the ligaments of the spinal cord

A
  • Anterior and posterior longitudinal ligaments – run the length of the spinal cord, prevents hyperflexion and hyperextension
  • Interspinous ligament – attach processes of adjacent vertebrae
  • Supraspinous ligament – attach tip of spinous processes of adjacent vertebrae
  • Ligamentum Flavum – extends between lamina of adjacent vertebrae
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136
Q

What is an intervertebral disc herniation?

A

Annulus Fibrosus no longer contains the Nucleus Pulposus and it bulges into the spinal canal or intervertebral foramina

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137
Q

Why are straight posterior herniations usually prevented?

A

Prevented by the posterior longitudinal ligament

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138
Q

What type of herniation is more common?

A

Herniation into the intervertebral foramina

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139
Q

What part of the spinal cord do hernias occur most commonly?

A

Lumbar

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140
Q

What is a spinal cord segment?

A

Area of the spinal cord from which a pair of spinal nerves are given off

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141
Q

How many spinal nerve are there?

A

31 pairs

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142
Q

How many pairs of spinal are there in each spinal segment?

A 
o	8 Cervical
o	12 Thoracic
o	5 Lumbar
o	5 Sacral
o	1 Coccygeal
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143
Q

What are the two roots and what do they carry?

A
  • Dorsal root – carries sensory fibres and has a dorsal root ganglion which houses the cell bodies
  • Ventral root – carries motor fibres
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144
Q

Name some neuronal markers and where they can be found

A
  • Nucleus – NeuN
  • Axons – phosphorylated neurofilament
  • Cell bodies- non phosphorylated neurofilament
  • Cell bodies and dendrites – MAP-2
  • Synapses – synaptophysin
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145
Q

Name some proteins that can be stained in astrocytes

A

o GFAP
o S100beta
o Glutamine synthetase
o Holzer

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146
Q

Name the three layers of blood vessels

A

Adventitia, media, intima

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147
Q

Name some proteins that can be found in the epithelia of blood vessels

A

CD34, CD31, vWF

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148
Q

Name two proteins of the basement membrane of blood vessels

A

Collagen IV, PASD

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149
Q

Define gene

A

Any interval along the chromosomal DNA that is transcribed into a functional RNA molecule or that is transcribed into RNA and then translated into a functional protein

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150
Q

What are the different patterns of inheritance?

A

Autosomal dominant - mutant allele found in one copy and causes disease

Autosomal recessive - two copies of mutant gene to cause disease

X-linked recessive - more common in males

Sex linked dominant - rare

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151
Q

Why are males more commonly affected by x-lined recessive disorders? and why can females also be affected?

A

Males only have one x chromosome so this will always be dominant

In females one x chromosome is usually switched off in certain tissues causes lesser symptoms

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152
Q

What is incomplete penetrance?

A
  • Not always clear pattern of inheritance
  • Other genes can sometimes mask the mutant gene in a generation
  • This can then be passed on to the next generation – it appears a dominant mutation has skipped a generation
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153
Q

What are they potential rearrangements of chromosomes?

A
  • Balanced translocations
  • Duplications
  • Deletions
  • Inversions
  • Aneuploidies
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154
Q

What is population genetics?

A
  • Using statistical analysis to investigate genes
  • Linkage analysis
  • Slow process
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155
Q

What is the central dogma?

A
  • Describes the two-step process of transcription and translation
  • Information of genes into proteins
  • DNA to RNA to Protein
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156
Q

Why is there significantly more proteins than genes?

A

Alternative splicing

- Different exons can be included or excluded giving rise to different mRNA molecules and different proteins

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157
Q

What are the four epigenetic changes that can change gene expression?

A

Methylation
o Methyl groups added to DNA molecule – typically acts to repress transcription
o Often at cytosine in region of DNA molecule associated with promotion of transcription
o Can be transmitted between generations

Histone acetylation

Non-coding RNA
o Have a role into determining whether RNA is transcripted and transcribed

RNA editing
o DNA code does not math RNA
o Post-transcriptional process leads to possible altered protein
o Particularly important in Neuroscience
o Often result of action of ADARs

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158
Q

What are restriction endonucleases?

A
  • Enzymes, mostly extracted from bacteria where they protect against viruses by cleaving the foreign DNA from the cell
  • Cleave DNA at specific sites
  • Cut sequences out – called palindromes
  • Creates sticky ends in which a new fragment of DNA can be added by complementary base pairing
  • Important part of recombinant DNA technology – replacing faulty genes with functioning ones
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159
Q

What is a southern blot?

A
  • Used to locate as specific sequence of DNA within a complex mixture
  • E.g. it could be used to identify a specific gene in an entire genome
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160
Q

What are cDNA libraries?

A
  • Complementary DNA library
  • Collection of only the genes that code for a protein
  • Created through reverse transcription of messenger RNA
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161
Q

What are vectors?

A
  • A DNA molecule used as a vehicle to artificially carry foreign genetic material into another cell, where it can be replicated and/or expressed
  • E.g. Bacterial plasmid
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162
Q

What is in situ hybridisation?

A
  • Localisation of probe on chromosome spread

- Used to located position of genes and other DNA sequences on RNA

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163
Q

What is a DNA probe?

A

Short sequences of single stranded DNA that match a portion of the gene that is being looked for

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164
Q

What is FISH?

A

o Fluorescent in situ hybridisation

o Label the probes with fluorescent dyes so they can be seen under a microscope

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165
Q

What is positional cloning?

A
  • Used to locate the position of a disease associated gene along a chromosome
  • Family linkage analysis identifies genetic markers which indicates a chromosomal region in which the gene could be located
  • Many genes for conditions have been located via this method (e.g. cystic fibrosis
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166
Q

What is a microarray?

A
  • Looking at the expression of thousands of genes at the same time
  • mRNA molecules are collected from both an experimental sample and a reference sample
  • Then converted into cDNA and labelled with a fluorescent probe of a different colour
  • Both samples are mixed together where cDNA bind to DNA probes on the slide
  • Then analysed to see if there is a mismatch in expression of certain genes when the samples are compared
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167
Q

What can and cannot cross biological membranes without the help of transporters?

A
  • Small uncharged molecules – low degree of crossing
  • Large uncharged molecules and ions – impermeable
  • Ion channels/transporters are required for ion movements
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168
Q

What is an action potential?

A

Transient alterations in membrane potential that propagate along axons

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169
Q

What are the possible consequences of an action potential?

A 
o	Synaptic vesicle release (Neurons)
o	Hormone releasing (endocrine cells)
o	Contracting (muscle cells)
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170
Q

What is the resting membrane potential?

A

-70mv

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171
Q

What is the equilibrium potential and how does it become established?

A

Equilibrium potential – the potential difference across the membrane at the equilibrium point for a specific ion

  • Potassium diffuses out of the cell (concentration gradient)
  • A slight excess of negative charge will therefore build up on the inner face of the membrane – this generates a growing electrical field and attracts potassium back in (electrical gradient)
  • The rate of potassium efflux (down the concentration gradient) is exactly counterbalanced by potassium influx (down the electrical gradient) and there is not net movement (Equilibrium point)
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172
Q

How is the resting membrane potential established?

A
  • Mainly due to the efflux of K+ which diffuse out of the cell via leak channels
    o Driven by passive diffusion
    o K+ has a higher concentration inside the cell than it does out

Membrane most permeable to K+

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173
Q

What is the Nernst equation?

A

Used to work out the equilibrium potential of a specific ion

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174
Q

What is the equilibrium potential for K+

A

-90mv

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175
Q

Why is the resting membrane potential around -70mv?

A
  • Close to the equilibrium potential of potassium due to the membrane being 50-100 times more permeable to K+ than to other ions
  • Other ions have a small effect so resting potential is not exactly -90mv
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176
Q

What is the goldman equation?

A
  • Combines the equilibrium potentials for each of the main ions in a single expression
  • Gives a predicted membrane potential difference
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177
Q

Why is the relative permeability of each ionic species factored into the goldman equation?

A

o If the membrane were mostly permeable to one particular ion, then the membrane would be closer to the equilibrium potential of that ion
o If there were two main ionic species of equal permeability, the membrane potential would be halfway between the two equilibrium potentials

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178
Q

What is a graded potential?

A
  • Local depolarisation of the cell membrane in response to a stimulus
  • Size and duration are proportional to the stimulus responsible for it
  • If a graded potential is sufficiently strong it may trigger an action potential
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179
Q

What is a receptor potential?

A

Graded potentials generated by sensory receptor cells in the PNS

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180
Q

What can an action potential be initiated by?

A

o Neuronal cell body – excitatory and inhibitory influences from other nerve cells have been integrated
o Sensory nerve endings – in response to a sufficiently strong graded potential (triggered by mechanical, thermal, or other forms of stimulation)

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181
Q

Why is an action potential described as an all or nothing response?

A
  • To trigger an action potential a threshold potential must be reached
  • Once this is reached a full action potential will occur
  • Not possible for an action potential to vary in magnitude like a graded potential – it either occurs or it does not (all or none law)
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182
Q

What value is the threshold potential typically?

A

-55mv

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183
Q

How is intensity of a stimulus encoded by?

A
  • Amplitude of the action potential does not vary
  • Intensity of a stimulus is encoded by the frequency of nerve impulse traffic
  • Frequency modulated rather than amplitude modulated
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184
Q

What are the two types of refractory periods?

A

Absolute and relative

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185
Q

What is the absolute refractory period?

A

The interval in which is not possible to trigger a second action potential to trigger a second action potential regardless of stimulus strength

is due to inactivation of the voltage gated sodium ion channels – do not reopen until membrane is repolarised

186
Q

What is the relative refractory period?

A

The interval in which a second action potential can be generated, but only with a stronger stimulus than usual

due to the undershoot (hyperpolarisation)

187
Q

Describe the ionic bases of the action potential

A
  • At rest – voltage gated N+ and K+ channels are closed but responsive
  • Depolarisation (rising) phase – N+ channels open, K+ channels remain closed
  • Maximum depolarisation (overshoot) – N+ channels inactivate, K+ channels open
  • Repolarisation (falling) phase – K+ channels open, Na+ channels remain inactivated
  • At rest – Na+ channels reset, both channels closed but responsive
  • After-hyperpolarisation
    o Occurs because some of the delayed rectifiers are still open and the membrane is more permeable to K+ than it was at rest
    o Membrane potential is closer to the equilibrium potential of K+ (-90mv)
188
Q

Where are channels and transported concentrated on a myelinated axon?

A

Nodes of Ranvier

189
Q

What is saltatory conduction?

A

action potential jumps from node to node

190
Q

What are the main components of the brainstem?

A
  • Midbrain
  • Pons
  • Medulla oblongata
191
Q

What are the crus cerebri?

A

columns of descending fibres of the corticospinal tract, converge as they meet the pons

192
Q

What is the interpeduncular fossa?

A

separates the peduncles anteriorly in the midline

193
Q

What is the tectum and the tegmentum of the midbrain?

A
  • Tectum – The midbrain dorsal to the cerebral aqueduct – made up of the colliculi
  • Tegmentum – The midbrain ventral to the aqueduct – made up of nerve fibres entering and leaving the cerebral hemispheres, nerve nuclei etc
194
Q

What are the two paired colliculi and what are they involved with? Describe their connections

A
  • Superior colliculi – part of the visual system, concerned with eye movements
    o Connected to the lateral geniculate body in the thalamus via the superior brachium
  • Inferior colliculi – part of the auditory system concerned with the reflex of looking towards a noise
    o Connected to the medial geniculate body via the inferior brachium
195
Q

What is the pineal gland?

A

an endocrine gland that synthesis melatonin - involved in circadian rhythms

196
Q

What tracts are present in the crus cerebri?

A

o Frontopontine fibres – most medial
o Corticospinal fibres – motor fibres from the cerebral cortex
o Corticobulbar tracts – motor fibres from the primary motor cortex
o Temporopontine fibres – located posterolaterally

197
Q

Where is the substantia nigra located?

A

separates the regions of the cerebral peduncles

198
Q

What are the two regions of the substantia nigra?

A

Split into the pars reticula (anteriorly) and pars compacta (posteriorly)

199
Q

What is the periaqueductal grey and what does it contain?

A

grey matter that surrounds the cerebral aqueduct

Contains the nuclei of the trochlea and oculomotor nerves

200
Q

What is the red nucleus?

A

Located in the central portion of the midbrain, involved with coordination of muscle tone, body position and gait

201
Q

What is the transverse groove at the caudal of the pons called?

A

Bulbopontine sulcus

202
Q

What cranial nerve nuclei are located in the tegmentum of the pons?

A

Abducens (CN VI), facial (CN VII) and trigeminal (CN V) cranial nerves

203
Q

What are the pontine nuclei responsible for and where are they located?

A

Responsible for coordinating movement and are located in the ventral pons

204
Q

What is the reticular formation?

A

A set of nuclei found throughout the brainstem that are responsible for arousal and attentiveness

205
Q

What can damage to the reticular formation result in?

A

Anosognosia for hemiplegia – where patients are unaware of their paralysis

206
Q

What tracts pass through the pons and what are they responsible for?

A

o Descending corticospinal tracts – responsible for voluntary motor control of the body
o Descending corticobulbar tracts – responsible for voluntary motor control of face, head and neck
o Ascending medial lemniscus tracts – responsible for fine touch, vibration and proprioception
o Ascending spinothalamic tracts – responsible for pain and temperature sensation

207
Q

What cranial nerve nuclei are located in the pons?

A

CN V (trigeminal), VI (Abducens), VII (facial), VIII (vestibulocochlear)

208
Q

What is the partial division of the medulla in the ventral midline called?

A

Anterior median fissure

209
Q

What is a pyramid (in the medulla)?

A

an elongated eminence (swelling) marking the position of underlying fibres passing from the cerebral hemispheres to the cord

210
Q

What fibres are carried within the pyramids?

A

Corticospinal

211
Q

What is the decussation of the pyramids?

A

diagonally orientate bundles of fibres crossing the fissure via which about 80% of corticospinal fibres cross the midline to enter the opposite lateral white column of the spinal cord

212
Q

What is the ventrolateral sulcus and where is it located?

A

on the lateral border of the pyramid on each side, continuous with same groove in the spinal cord

213
Q

What is the olive and where is it located?

A

lateral to the ventrolateral sulcus, this eminence is caused by the presence of the underlying inferior olivary nucleus and is concerned with the control of movement

214
Q

What is the depression on the dorsal aspect of the medulla called?

A

Posterior median swelling

215
Q

What is the gracile and cuneate tubercles and where are they located in relation to each other?

A
  • Gracile tubercle – a round swelling on either side of the midline
  • Cuneate tubercle – a swelling lateral to the Gracile Tubercles
  • Overly the gracile and cuneate nuclei of the dorsal column
216
Q

What are the internal arcuate fibres?

A

run from the nucleus gracilis and the nucleus cuneatus around and anterior to central grey matter to form the medial lemniscus on the contralateral side

The decussation of the dorsal column pathway

217
Q

What is the name, exit, modality and function of CN I?

A

olfactory nerve

Cribriform plate of ethmoid

sensory

Smell

218
Q

What is the name, exit, modality and function of CN II?

A

Optic

Optic canal

sensory

Vision

219
Q

What is the name, exit, modality and function of CN III?

A

Oculomotor

Superior orbital fissure

Motor

Innervates medial rectus, superior rectus, inferior rectus and inferior oblique and levator palpebrae superioris (elevates the upper eyelid)

Innervates pupillary sphincter (constricts pupil)

220
Q

What is the name, exit, modality and function of CN IV?

A

Trochlear

Superior orbital fissure

Motor

Innervates superior oblique (stops double vision when looking down)

221
Q

What is the name, exit, modality and function of CN V(i)?

A

Ophthalmic branch of trigeminal

Superior orbital fissure

Sensory

Sensation to scalp, forehead and nose

222
Q

What is the name, exit, modality and function of CN V(ii)?

A

Maxillary branch of trigeminal

Foramen rotundum

Sensory

Sensation to cheeks, lower eyelid, nasal mucosa, upper lid, upper teeth and palate

223
Q

What is the name, exit, modality and function of CN V(iii)?

A

Mandibular branch of trigeminal

Foramen ovale

Sensory and motor

Sensation to skin over mandible, lower teeth and anterior 2/3rds of tongue

Motor to muscles of mastication (temporalis)

224
Q

What is the name, exit, modality and function of CN VI?

A

Abducens

Superior orbital fissure

Motor

Innervates lateral rectus

225
Q

What is the name, exit, modality and function of CN VII?

A

Facial

Internal acoustic meatus –> stylomastoid foramen

Sensory and motor

Sensation to part of external ear

Taste from anterior 2/3 tongue

Muscles of facial expression

226
Q

What is the name, exit, modality and function of CN VIII?

A

Vestibulocochlear

Internal acoustic meatus

Sensory

Hearing and balance

227
Q

What is the name, exit, modality and function of CN IX?

A

Glossopharyngeal

Jugular foramen

Sensory and motor

Sensation and taste to posterior 1/3 of tongue

Visceral sensation from carotid body and sinus

Motor to stylopharyngeus

Parasympathetic fibres to parotid gland

228
Q

What is the name, exit, modality and function of CN X?

A

Vagus

Jugular foramen

Sensory and motor

General somatic sensation to external ear, larynx and pharynx

General visceral sensation to larynx, pharynx and thoracic and abdominal viscera

General visceral motor to smooth muscle of pharynx, larynx and most of GI tracts

Motor to most muscles of pharynx and larynx

229
Q

What is the name, exit, modality and function of CN XI?

A

Accessory

Jugular foramen

Motor

Innervates trapezius and sternocleidomastoid

230
Q

What is the name, exit, modality and function of CN XII?

A

Hypoglossal

Hypoglossal canal

Motor

Innervates intrinsic and extrinsic tongue muscles

231
Q

What are the two visual fields?

A

Nasal and temporal

232
Q

Which visual fields cross at the optic chiasm?

A

Temporal

233
Q

What are three components of the visual pathway?

A

Optic nerve, optic tract, optic radiation

234
Q

Describe the visual pathway

A

Optic nerve carries visual information from both eyes to the optic chiasm where the fibres from the temporal visual field cross over. Nasal visual field remains ipsilateral

This forms the optic tracts which synapse in the lateral geniculate body of the synapse

From here two optic radiations travel to the primary visual cortex in the occipital lobe

235
Q

What is meyer’s loop and what information does it contain?

A

Optic radiation from the thalamus to the visual cortex that passes through temporal lobe

Carries information from the lower retina (and therefore the upper visual field)

236
Q

What are the two optic radiations and what neurons do they contain?

A

Optic radiation carrying neurons from the upper retina (lower visual field) passes through the parietal lobe and neurons from the lower retina pass through the temporal lobe

237
Q

What does damage to the optic chiasm result in (e.g. pituitary tumour)?

A

Bitemporal hemianopia

238
Q

What does damage to meyer’s loop result?

A

Upper quadrantanopia (ipsilateral to lesion)

239
Q

What are the contents of the diencephalon?

A
  • Contains the epithalamus, thalamus, hypothalamus and the subthalamus.
    o Grey matter either side of the third ventricle
  • Epithalamus contains the pineal gland and posterior commissure amongst other things
240
Q

What does the internal capsule separate?

A

the caudate nucleus and thalamus from the globus pallidus and the putamen

241
Q

What is the corona radiata?

A

white matter fibres that radiate from the narrow internal capsule to the cerebral cortex

242
Q

What is the Centrum semiovale?

A

mass of white matter superior to the lateral ventricles and corpus callosum, present in each cerebral hemisphere

Continuous with corona radiata inferolaterally

243
Q

What are the two sides of the thalamus sometimes connected by?

A

Massa intermedia

244
Q

What are the three main groups of nuclei in the thalamus ?

A

o Sensory relays
o Cerebellar and basal ganglia relays to motor frontal lobe
o Connected to associative and limbic areas of cerebral cortex

245
Q

Name the parts of the basal ganglia

A
  • Putamen
  • Globus pallidus (lateral and medial part)
  • Caudate nucleus
  • Thalamus
  • Subthalamic nucleus
  • Substantia nigra
246
Q

What makes up the corpus striatum?

A

Caudate and lentiform nuclei

247
Q

Whats makes up the lentiform nucleus?

A

Putamen and globus pallidus

248
Q

What are the two functional divisions of the basal ganglia and what do they contain?

A

Striatum – Caudate nucleus and putamen
o The input portion which receives projections from the overlying cerebral cortex

Pallidum – in particular the internal segment of the globus pallidus
o The output portion which project to the thalamus

249
Q

Describe the direct pathway of the basal ganglia

A

Normal resting state – internal part of the globus pallidus (GPi) and Substantia Nigra pars reticular (SNpr) are inhibiting the thalamus

When you decide to move – frontal lobes send an excitatory signal to the striatum
o Neurotransmitter = glutamate

The neurons in the striatum then send an inhibitory signal to GPi and SNpr and are no longer inhibiting the thalamus

The thalamus is un-inhibited, and movement can then occur

250
Q

Where is dopamine secreted?

A

Secreted by the substantia nigra pars compacta

251
Q

What is the role of dopamine in the direct pathway?

A

Dopamine interacts with the D1 receptors of cells in the striatum

Dopamine has a stimulatory effect via the D1 receptor so causes the striatum to be more active furthing inhibiting the globus pallidus and substantia nigra pars reticulata

Results in more movement

252
Q

Describe the indirect pathway of the basal ganglia

A

Inhibits movement
o Helps prevent unwanted muscle contractions from competing with voluntary movements

Excitatory signals from the motor cortex are sent to the striatum

Striatum sends inhibitory signals to the globus pallidus externus
o Globus pallidus externus normally sends inhibitory signals to the subthalamic nucleus

On activation of the indirect pathway these inhibitory signals are reduced – allows more activation of the subthalamic nucleus

The subthalamic nucleus can then send more activating signals to the globus pallidus internus and substantia pars reticulata
o Driven to send more inhibitory signals to the thalamus which prevents movement

253
Q

What is the role of dopamine in the indirect pathway?

A

Acts on D2 receptors of the striatum

Causes striatal neurons to decrease their inhibitory signals to the globus pallidus externus

Globus pallidus externus free to carry out its normal function

Results in less inhibition of the thalamus – more movement

254
Q

What is the limbic lobe and insula and what are they concerned with?

A
  • Ring-shaped convolution surrounding the medial border of the cerebral hemispheres
  • Concerned with emotion and memory
255
Q

Where is the cingulate gyrus located?

A

Cingulate gyrus wraps around the corpus callosum on the medial surface of the cerebral hemisphere

Separated from the frontal lobe by the cingulate sulcus

256
Q

What is the uncus?

A

a hook-shaped fold of cortex that marks the end of the parahippocampal gyrus

257
Q

Where is the insula located?

A

Forms the floor of the lateral ventricle – can be exposed by retracting the overhanging opercula of the frontal, parietal and temporal lobes

258
Q

What is the insula divided into and what are their functions?

A

Anterior insula – receives input from the olfactory bulb and is part of the primary olfactory cortex
o Also involved in nausea, vomiting, disgust and pain perception

Posterior insula – integrates non-visceral (somatic) information related to touch, vision and hearing

259
Q

Where is the hippocampus located and what is its function?

A

Occupies the temporal horn of the lateral ventricle

Consists of the dentate gyrus and Ammon’s horn (Hippocampus proper)
o Ammon’s horn contains large pyramidal neurons arranged into three zone (CA1, CA2, CA3)

Involved with the formation of new memories

Particularly important for the recollection of personal memories (episodic memory)

260
Q

What are the structures in the papez circuit?

A 
o	Hippocampus and adjacent cortex (entorhinal cortex)
o	Fornix
o	Mammillary bodies
o	Anterior nucleus of the thalamus
o	Cingulum
261
Q

What are mossy fibres?

A

Axons of dentate granule cells

262
Q

Describe the perforant path

A

Afferent projections into the hippocampus originate in the entorhinal cortex

Terminates on granule cells in the dentate gyrus

Axons of dentate granule cells (Mossy fibres) project in turn to CA3 pyramidal cells

The intrinsic connections of the hippocampus also project back to the entorhinal cortex to a form a closed loop – important in memory formation

263
Q

Describe the Papez circuit

A

1) Entorhinal cortex
2) Hippocampus
3) Fornix
4) Mammillary body
5) Mammillothalamic tract
6) Anterior thalamus
7) Internal capsule
8) Cingulate gyrus
8) Cingulum
9) Entorhinal

264
Q

What is the amygdala?

A

Almond shape mass of grey matter in the anterior part of the medial temporal region. Lies just in front of the hippocampus

265
Q

What is the function of the amygdala?

A

Danger detector

  • Involved in all types of emotional response but is particularly important in situations that illicit anxiety, fear or rage
  • Integrates diverse sensory, cognitive, and other information to help determine the emotional significance of a particular situation
  • Important role of identification of potentially harmful circumstances and triggering appropriate autonomic responses (e.g. a fight or flight reaction)

Also involved in implicit learning - particularly during emotionally charged situations

266
Q

What are the two hemispheres of the cerebellum joined by?

A

The vermis

267
Q

Name the lobes of the cerebellum

A
  • Anterior lobe – bordered by the primary fissure posteriorly
  • Posterior lobe – bordered by the primary fissure anteriorly and the horizontal fissure posteriorly
  • Flocculonodular lobe – the flocculus and the nodule together
268
Q

What two fissures can be seen on the superior surface of the cerebellum?

A

Horizontal fissure – marks the lateral and posterior margins of the hemisphere
o The fissures and folia of the superior surface curve from the postero-medial to antero-lateral to converge on the horizontal fissure

Primary fissure – considerably deeper and more conspicuous than the other fissure
o Marks the division between the anterior and posterior lobes of each cerebellar hemisphere

269
Q

What is the tonsil of the cerebellum?

A

a prominent round swelling of the cerebellar cortex anteriorly on either side of the vermis

270
Q

What are the functional divisions of the cerebellum and what are they involved with?

A

Cerebrocerebellum – the largest division, formed by the lateral hemispheres
o Involved in planning movements and motor learning
o Receives inputs from the cerebral cortex and pontine nuclei
o Sends outputs to the thalamus and red nucleus
o Also regulates coordination of muscles activation and is important in visually guided movements

Spinocerebellum – comprised of the vermis and intermediate zone of the cerebellar hemispheres
o Involved in regulating body movements by allowing for error correction
o Also receives proprioceptive information

Vestibulocerebellum – functional equivalent to the Flocculonodular lobe
o Involved in controlling balance and ocular reflexes – mainly fixation on a target
o Receives inputs from the vestibular system
o Outputs back to the vestibular nuclei

271
Q

What are the three cerebellar peduncles and what do they connect?

A
  • Superior – midbrain
  • Middle – pons
  • Inferior – medulla
272
Q

What are the connections of the cerebellum and how do they enter it?

A

Spinocerebellar tracts – sensory input for balance and position sense from spinal cord
o Dorsal spinocerebellar – ipsilateral via inferior cerebellar peduncle
o Ventral spinocerebellar – contralateral via superior cerebellar peduncle

Corticopontocerebellar - information from the primary motor cortex of the motor plan, the same information goes to the spine
o Enters via middle cerebellar peduncle

Vestibulocerebellar tract – vestibular impulses from labyrinths
o Directly and via the vestibular nucleus
o Enters via the inferior cerebellar peduncle

273
Q

What are the cerebellar nuclei and what are they involved with?

A

Fastigial nuclei – most central pair and are associated with the vermis
o Maintenance of balance

Globose and emboliform nuclei – referred to as the interposed nucleus
o Regulation of skilled muscle tone and flexor motor activity of the ipsilateral side

Dentate nucleus – largest and is situated in the lateral hemispheres
o Important for the regulation of many aspects of voluntary motor activity – namely its timing, planning and inception
o Major fibre bundles pass into the superior cerebellar peduncle
o Only nucleus that can be clearly identified on a specimen

274
Q

What are the three layers of the cerebellar cortex?

A

Molecular layer
Purkinje cell layer
Granular layer

275
Q

What does the uppermost layer of the cerebellar cortex contain?

A

o Contains very few cell bodies
o Dendritic trees of the Purkinje cells extend into this area and interact with the axons of granule cells
o Parallel fibres of granule cells synapse with numerous Purkinje dendritic tress – uses glutamate to have an excitatory effect

276
Q

What does the middle layer of the cerebellar cortex contain?

A

o Contains Purkinje cells bodies
o Sole efferent pathway from the cerebellum
o Provides inhibitory impulses to vestibular and cerebellar nuclei
o Purkinje cells are excited by climbing fibres of the inferior olivary nucleus and parallel fibres of the granule cells

277
Q

What does the deepest layer of the cerebellar cortex contain?

A

o Houses the granule and Golgi
o Granule cells are inhibited by Golgi cells but are excited by mossy fibres
o Mossy fibres – afferent branches of the pontocerebellar and spinocerebellar tracts

278
Q

What is the Rhomboid Fossa?

A

diamond shaped floor of the IVth ventricle limited laterally by the cerebellar peduncles and posteriorly by the gracile and cuneate tubercles

279
Q

What separates the rhomboid fossa?

A

Median sulcus separates into triangular left and right halves

280
Q

What is the facial colliculus?

A

rounded swelling on the dorsal pons caused by fibres of CN VII as they loop over the abducens nerve

281
Q

What is the medullary striae?

A

Ponto-cerebellar fibres (which form a portion of the cochlear division of the vestibulocochlear nerve). Divide the floor of the ventricle into a rostral pontine half and a caudal medullary half

282
Q

What is the sulcus limitans?

A

separates the cranial nerve nuclei (Medial) from the sensory nuclei (lateral)

283
Q

What is the locus coeruleus

A

bluish-grey pigment nor-adrenergic cells (principle site of noradrenaline synthesis in the brain) under the Ependyma at the Rostral half of the Sulcus limitans

284
Q

What are the three trigones?

A
  • Hypoglossal trigone – medial triangular area overlying the XIIth nerve nucleus
  • Vagal trigone – intermediate triangular area overlying the Xth nerve nucleus
  • Vestibular trigone – lateral triangular area overlying the VIIIth nerve nucleus
285
Q

What is the obex?

A

inferior apex of the rhomboid fossa

286
Q

What is the area postrema and where is located?

A

small tongue-shaped area immediately rostrolateral to the Obex

Commonly associated with nausea control – a chemoreceptive trigger zone for the emetic response

287
Q

What is the third ventricle?

A

narrow slit like cavity lying in the midline between the two halves of the Diencephalon

288
Q

What is the third ventricle bordered by?

A

o Bordered anteriorly by the Lamina Terminalis, above by Tela Choroidea, below by the optic chiasm, pituitary stalk, Mammillary bodies and tegmentum of the midbrain

289
Q

What is the paracentral lobule and what does it contain??

A

a U-shaped gyrus surrounding the medial extension of the Central sulcus

Contains the representations of the lower limb within the primary motor and somatic sensory areas

290
Q

Where is the calcarine sulcus located and what it contain?

A

Roughly at right angles to the Parieto-occipital sulcus, it runs posteriorly to reach the occipital pole

Primary visual cortex lies in the walls of the calcarine sulcus

291
Q

What is the striae of Genari?

A

white band in the primary visual cortex running parallel with the pial surface in the mid-depth of the grey matter (gives the name striate cortex to the primary visual area)

292
Q

What are the sections of the corpus callosum?

A

o Genu – the anterior cured end
o Rostrum – leads downwards from the genu
o Body – the central main curve
o Splenium – the rounded posterior end

293
Q

What is the fornix and what does it connect?

A

Bundle of white matter beneath the body of the corpus callosum

Connects the hippocampus with diencephalon and the precommissural septum

294
Q

What is the commissure of the fornix?

A

Fibres from one hippocampus cross to the opposite Fornix and to the opposite hippocampus

295
Q

What are the columns of the fornix?

A

anterior and posterior extensions, anteriorly they extend vertically downwards to the mammillary bodies

296
Q

What is anterior commissure and what does it connect?

A

Thick bundle of white matter crossing the midline horizontally between the lamina terminalis and fornix

Crosses to interconnect the temporal lobes and olfactory structures of each side

297
Q

What is the septum pellucidum?

A

Two thin vertical sheets made primarily of glia with a few white fibres, sparse grey matter and covering of ependyma

Separates the anterior horns of the lateral ventricles

298
Q

What is the lamina terminalis?

A

thin sheet of ependyma and pia which extends downwards from the rostrum of the callosum and fornix to the anterior wall of the third ventricle

299
Q

What is the thalamus?

A

Major subcortical relay for information ascending to the cerebral cortex

300
Q

What is the interthalamic adhesion?

A

Joins the thalamus of each side, may be absent

301
Q

What is the hypothalamic sulcus?

A

Shallow groove on the lateral wall of the third ventricle extending from the cerebral aqueduct to the interventricular foramen

302
Q

What does the medial geniculate body do?

A

relays auditory information from midbrain to the auditory cortex and passes some fibres via the inferior brachium to the inferior colliculi

303
Q

What does the lateral geniculate body do?

A

Relays visual information from the optic nerve to both the visual cortex via the optic radiation (for vision) and via the superior colliculi via the superior brachium (for pupillary reflexes)

304
Q

What are the three types of the fibres in the brain?

A
  • Association fibres – link cortical regions within one hemisphere
  • Commissural fibres – link similar functional areas of the two hemispheres
  • Projection fibres – link the cortex with subcortical structures such as the thalamus and spinal cord via the internal capsule and to Corona Radiata
305
Q

What is the anterior perforated substance?

A

quadrilateral area of grey matter, lateral to optic chiasm

306
Q

Briefly describe the olfactory system

A

Olfactory nerve – CN I, enters through the cribriform plate, synapses in the olfactory bulbs

Olfactory tract – from the olfactory bulbs, runs on the orbito-frontal surface of the brain

Olfactory striae –The olfactory tract divides into medial and lateral (most of the fibres) striae along the anterior border of the anterior perforated substance

The lateral stria runs to the uncus

307
Q

What is the superior longitudinal fasciculus?

A

largest bundle of association fibres, connects all four lobes of the brain

308
Q

What is the cingulum bundle?

A

projects from the cingulate gyrus to the entorhinal cortex

309
Q

Name the parts of the lateral ventricle

A
  • Anterior horn – curves downward into the frontal lobe from the interventricular foramen
  • Body – roofed over by the main part of the corpus callosum, fornix and septum form the medial wall
  • Temporal (inferior) horn – the floor of the inferior horn is broad posteriorly but narrows as it passes forward
  • Posterior horn – the variable extension of the lateral ventricle into the occipital lobe
310
Q

What is the caudate nucleus?

A

has a head, body and tail and forms a large bulge into the anterior horn

Part of the basal ganglia

311
Q

What is the striae terminalis?

A

a slender bundle of white fibres accompanying the curve of the caudate around into the temporal horn

Connects the amygdala with the septum and hypothalamus

312
Q

What are fimbria?

A

efferent fibres from the hippocampus heading to the fornix forming a flattened, longitudinal bundle of white matter on the medial margin of the ventricular surface of the hippocampus

313
Q

What is the claustrum?

A

Forms part of the basal ganglia

Receives from and projects to the cerebral cortex in a topographically organised manner

Known to have cells within it which respond to visual, auditory, and sensory stimuli

Located between the external capsule and extreme capsule

314
Q

What is the external capsule?

A

white matter separating the claustrum from the putamen

315
Q

What is the lateral medullary lamina?

A

white matter between the Putamen and the lateral segment of the globus pallidus

316
Q

What is the medial medullary lamina?

A

white matter separating the lateral (external) and medial (internal) segments of the globus pallidus

317
Q

What is the nucleus accumbens and where is it situated?

A

The reward centre of the brain

Situated between the caudate and the putamen

318
Q

What is the forceps major?

A

posterior curve of the fibres of the genu of the corpus callosum into the parietal and occipital lobes

319
Q

What is the forceps minor?

A

anterior curve of the fibres of the genu of the corpus callosum into the frontal lobe

320
Q

What is parkinson’s disease?

A

Degeneration of dopaminergic neurons of the pars compacta of the substantia nigra with depletion of striatal dopamine levels

321
Q

What are the symptoms of Parkinson’s?

A 
o	Cog-wheel rigidity
o	Pill-rolling tremor at rest
o	Shuffling, festinated gait 
o	Bradykinesia
o	Loss of facial expressions
322
Q

What is Huntington’s disease?

A

Autosomal dominant disease due to degeneration of the corpus striatum (caudate, globus pallidus, putamen) and cerebral cortex

323
Q

What are the symptoms of Huntingdon’s?

A

o Chorea
o Personality change
o Depression
o Progressive dementia

324
Q

What is a lacunar stroke?

A

Occlusion of a deep perforating artery, the resultant lesions occur in the deep nuclei, pons or internal capsule

325
Q

What can a stroke affecting the internal capsule cause?

A

o Hemiparesis typically affecting half the face, one arm or leg
o Ataxic hemiparesis (combination of cerebellar and motor symptoms) most commonly affecting the leg
o Mixed sensorimotor stroke if the thalamus is also affected, causing hemiparesis with ipsilateral sensory impairment

326
Q

Describe the role of the Na+/K+ ATPase pump

A
  • Helps maintain electrochemical gradients for Na+ and K+
  • 3 Na+ out and 2 K+ in per cycle
  • Electrogenic – requires energy
  • Uses ATP
  • 20-40% of brain energy expenditure
327
Q

What is the sodium potassium pump inhibited by and what does this cause?

A

o Inhibited by cardiac glycosides digoxin and ouabain

o Increase force of heart contraction by elevating intracellular Ca2+ (secondary effect, via Na+/Ca2+ exchanger

328
Q

Describe the structure of the sodium potassium pump

A

o Integral membrane protein alpha & β (& γ) subunits
o alpha 10 TM helices, mainly cytoplasmic
o β single TM helix
o Nucleotide-binding (N), phosphorylation (P) & actuator (A) domains

329
Q

Name another ATPase pump

A

Ca2+ ATPase

Maintains huge electrochemical Ca2+ gradient

330
Q

Name four types of ion channels

A

Voltage gated
Ligand gated
Heat sensitive
Mechanosensitive

331
Q

Describe the patch clamp method

A

o A single channel is extracted from a living cells, together with a small patch of the surrounding membrane
o Achieved by applying suction to microscopic pipettes
o Recordings from single ion channels show that during gating the pore is not simply open or closed but rapidly alternates between the two

332
Q

Describe the general voltage gated channel structure and its method of action

A
  • Are integral membrane proteins
  • Repeating motif with six membrane spanning alpha helices
  • Also, a pore loop that contributes to the selectivity filter (only allows certain ions through) and a charged domain that acts as a voltage sensor
  • During depolarisation the inner face of the cell membrane becomes more positive and the voltage sensor (which carries a positive charge) is thrust upwards through the membrane by electrostatic repulsion
  • Movement induces a conformational change which opens the pore
333
Q

Name some sodium channelopathies and what they are associated with

A
  • SCN1A – epilepsy, migraine, autism
  • SCN2A – epilepsy, autism, episodic ataxia
  • SCN3A – epilepsy
  • SCN9A – pain insensitivity & extreme pain disorder
334
Q

Name some potassium channelopathies and what they are associated with

A

KCNQ2, KCNQ3, KCNMA1 associated epilepsy syndromes

KCNA1 associated with episodic ataxia type 1

335
Q

Name some calcium channelopathies and what they are associated with

A
  • CACNA1A - episodic ataxia type 2, SCA6 and familial hemiplegic migraine
  • CACNA1B - myoclonus-dystonia syndrome
  • CACNA1F - X-linked congenital stationary night blindness
  • CACNA1H - childhood absence epilepsy
336
Q

What can mutations in the genes coding for channels affect?

A

o Channel assembly and/or function
o Pore permeability increased or decreased
o Inactivation

337
Q

Describe odorant receptors and what are they an example of?

A

o G-protein coupled receptors
o Activate adenylyl cyclase
o Cyclic-nucleotide gated Na+/Ca2+ channel
o Ca2+ activated chlorine channel

Ligand gated ion channel

338
Q

What are ligand gated ion channels activated by? Provide examples

A

Activated by second messengers

e.g. ions. neurotransmitters, cyclic nucleotides (cAMP, cGMP), H+ (pH), temperature

339
Q

What are the two classes of synapse?

A

Electrical - permit direct passive flow of current from one neuron to another

Chemical - use chemicals (neurotransmitters) to stimulate post-synaptic electrical flow

340
Q

What makes electrical synapses different from chemical synapses?

A 
o	Fewer
o	Bidirectional
o	Faster
o	Narrower
o	Less tightly regulated 
o	Enable synchronous firing of networks
341
Q

Are neurons linked in electrical synapses?

A

Linked by gap junctions called connexons

342
Q

Name some examples of electrical synapses

A

o Invertebrate escape response circuits (e.g. crayfish)
o Respiratory centre neurones (brainstem)
o Hypothalamic endocrine neurons

343
Q

What are the criteria that define a neurotransmitter?

A
  • Must be present within the presynaptic neuron
  • Must be released in response to depolarisation of the presynaptic neuron and release must be ca2+ dependent
  • Specific receptors must be present on postsynaptic cell
344
Q

What are the two classes of neurotransmitter? Name some examples

A

Small molecule neurotransmitters – short term effects
o Slow axonal transport – 0.5-5mm/day
o E.g. Amino acids, acetylcholine, purines, biogenic amines etc

Peptide neurotransmitters – longer term effects
o Fast axonal transport – up to 400mm/day
o E.g. Substance P, Vasopressin, CRH, ACTH, opioids, Neuropeptide Y etc

345
Q

What are the two types of synaptic vesicle and what can they contain?

A

Small clear vesicles
o Glutamate, GABA, Glycine, Acetylcholine, ATP etc

Dense-core vesicles
o Serotonin, histamine, neuropeptides, catecholamines

346
Q

What can synaptic vesicles differ in and what does this allow?

A

Differ in Ca2+ sensitivity

Allows differential release and therefore stimulus specificity

347
Q

What are two important types of SNARE proteins?

A
  • T-SNARE – connects to target membrane

- V -SNARE – connects to vesicle

348
Q

What are chaperones important for?

A

Important in breaking down and making complexes

349
Q

Describe the mechanism of membrane fusion of vesicles

A
  • Relies on a group of proteins belonging to the SNARE family
  • Vesicle and presynaptic membrane kiss and the interaction between complimentary proteins (SNARE) creates a small fusion pore
  • This quickly expands as the lipid membrane unite to form a large opening through which the contents of the vesicle are discharged into the synaptic cleft
  • After exocytosis – vesicle membrane becomes part of the presynaptic membrane
  • A similar amount of membrane is reclaimed from the axon terminal to make a new vesicle
    o No net increase in the size of the axon terminal
350
Q

What are SNARE proteins targets of and what can it cause?

A
  • Targets of Botulinum and Tetanus toxins
  • Cleave the snare proteins and thereby blocking neurotransmitter release
  • BoTX – mainly affects peripheral and visceral neuromuscular synapses
    o Weakness
  • TeTX – mainly affects inhibitory spinal interneurons
    o Tetanic contractions
351
Q

What can excess glutamate cause?

A

Excitotoxicity

352
Q

Name some specific inactivating enzymes

A

o Acetylcholinesterase (AChE)
o Monoamine oxidase (MAO)
o Catechol-O-methyltransferase (COMT)

353
Q

Describe some strategies for the up-regulation of neurotransmission and give examples

A

Give precursor of neurotransmitter
o E.g. L-DOPA in the treatment of Parkinson’s

Inhibit reuptake channels
o E.g. SSRIs in the treatment of depression

Inhibit inactivating enzymes
o E.g. acetylcholinesterase inhibitor in the treatment of myasthenia gravis

354
Q

Describe some strategies for the down-regulation of neurotransmission and give examples

A

Presynaptic – problem here is conserved nature of machinery
o Local application of Botox

Postsynaptic – block specific receptors
o E.g. antipsychotics target D2 dopamine receptors and other things – side effects

355
Q

What is the difference between excitatory and inhibitory amino acid neurotransmitters?

A
  • Excitatory – have 2 negative charges at physiological pH

- Inhibitory – have a single negative charge at physiological pH

356
Q

What are the two broad types of neurotransmitter receptor?

A

Ionotropic – open or close a channel to allow the movements of ions

Metabotropic – do not have a channel, linked to a G-protein which goes on to activate a secondary messenger

357
Q

What is GABA?

A
  • Main inhibitory NT in brain
  • Synthesised from glutamate by glutamic acid decarboxylase (GAD)
  • Loaded into synaptic vesicles by VIAAT
  • Cleared by GATS – Na+ dependent co-transporters
358
Q

Describe the two kinds of GABA receptors

A
  • GABAa inotropic – Cl- channels

- GABAb metabotropic – activate K+ channels or inhibit Ca2+ channels

359
Q

Briefly explain the pharmacology of GABA receptors

A 
o	GABAa receptor agonists widely used sedatives, anxiolytics, anti-convulsant, anaesthetics 
o	Barbiturates (e.g. pentobarbital) activate
o	Benzodiazepines (e.g. diazepam) enhance
o	Inhibitors (e.g. picrotoxin, PTZ) used experimentally as convulsants – animal models of epilepsy
360
Q

Describe the role of GABA in early development

A
  • GABA is excitatory in early development
  • Activity is needed to establish circuits
  • In immature CNS – high intercellular Cl- concentration compared to outside
    o Activation of GABAa receptor causes efflux of Cl- resulting in an action potential
  • In mature CNS – low intercellular Cl- concentration
    o Activation of GABAa receptor causes influx of Cl- - inhibitory
  • Changes in utero
361
Q

What is glycine?

A
  • Main inhibitory NT in spinal cord and brainstem
  • Glycine synthesis from Serine by serine hydroxyl-methyltransferase
  • Loaded into synaptic vesicles by VIAAT
  • Cleared by specific GlyT
    o Mutations give hyperglycinaemia (lethargy, seizures, MR)
362
Q

Describe glycine receptors

A
  • Inotropic, Cl- channels
  • 5 subunits, each have 4 transmembrane proteins
  • Clustered
  • Specifically inhibited by strychnine – induces seizures
363
Q

What are purine neurotransmitters?

A
  • ATP excitatory NT in CNS and PNS – MNs, sensory and autonomic ganglia
  • ATP rapidly catabolised to adenosine
    o Adenosine doesn’t meet NT criteria
364
Q

Describe purine receptors and what do they have a role in?

A

Ionotropic receptors for ATP (P2X), metabotropic receptors for ATP (P2Y) and adenosine (P1)
o Modulators may have a role as neuroprotective agents or for the treatment of chronic pain
o Also have non-CNS functions e.g. P2Y12 inhibitors are targeted by anti-platelet agents

365
Q

Name the three main catecholamines

A

Dopamine
Noradrenaline
Adrenaline

366
Q

Describe the synthesis of adrenaline (including enzymes)

A

L-Tyrosine to L-DOPA (Tyrosine hydroxylase (TH))

L-DOPA to Dopamine
(L-Aromatic amino acid decarboxylase (AAAD))

Dopamine to L-Noradrenaline
(Dopamine-beta-hydroxylase (DBH))

L-Noradrenaline to L-Adrenaline
(Phenylethanolamine-N-methyltransferase PNMT)

367
Q

What catalyses the synthesis of catecholamines?

A

MAO and COMT (targets of recreational drugs)

368
Q

Name a imidazoleamine

A

Histamine

369
Q

Name a indoleamine

A

Serotonin (5-hydroxytryptamine)

370
Q

Describe dopamines function and how this relates to disease

A
  • Movement – Parkinson’s disease
  • Motivation, reward and enforcement – drug addiction
  • Cognition and emotion
  • Schizophrenia – first antipsychotics led to dopamine theory
371
Q

What loads dopamine into vesicles?

A

H+ dependent VMAT

372
Q

What removes dopamine and what is it inhibited by?

A

Removed by DAT (Na+ dependent co-transporter) - inhibited by cocaine

373
Q

What are selegiline and rasagiline and what are they used for?

A

MAO-B inhibitors used in early PD

374
Q

What are COMT inhibitors used for? Name 2

A

Used with levodopa in PD

Entacapone and Tolcapone

375
Q

Describe dopamine receptors

A
  • All metabotropic
  • 2 classes – D1, D2, D3, D4, D5
  • Complex effects
    o Both excitatory and inhibitory
    o Depends on receptors and effectors
376
Q

Briefly describe the role of noradrenaline

A

Sleep, wakefulness and attention

377
Q

What is the main source of adrenaline in the CNS?

A

Medullary epinephrine neurons

378
Q

Describe adrenergic receptors and give an example of a drug that targets them

A
  • All metabotropic
  • Distributed through CNS and sympathetic nervous system
  • Alpha 1,2
  • Beta 1,2,3
  • Beta blockers – e.g. propranolol used to treat cardiac arrhythmias and migraines
379
Q

Describe the physiology of histamine

A
  • Roles include arousal and attention
  • Produced in tuberomammillary nucleus – located in hypothalamus
  • Metabotropic receptors – H1-H3
  • Antihistamines that cross BBB e.g. Promethazine (Blocks H1) acts as sedatives
380
Q

What is the role of serotonin?

A

Mood, sleep, wakefulness, nausea, appetite

Anti-depressants and axiolytics increase it

381
Q

What clears serotonin and what targets this?

A

Cleared by SERTs – targets of fluoxetine/Prozac, etc (SSRIs)

382
Q

Describe serotonin receptors

A

7 receptor subtypes – diverse effects

Mainly metabotropic – except 5-HT3 (Na+, K+, Ca2+ channel)

383
Q

Give some examples of serotonin pharmacology

A

Sumatriptan – 1F, 1B,1D receptor agonist
o Used to treat migraines

Ondansetron - HT 3 receptor antagonist
o Used for nausea and vomiting in chemotherapy

SSRI antidepressants - SERT inhibitor

Fenfluramine – SERT inhibitor
o withdrawn diet pill

LSD is an 2A, 2C receptor agonist

384
Q

Describe peptide neurotransmitters

A
  • Generally synthesised as pre-proproteins
  • Multiple neuroactive peptides can be released from a single vesicle
  • Complex responses in conjunction with small molecule neurotransmitters
  • Active at low concentrations
  • Metabotropic receptors
385
Q

Name some functions of peptide neurotransmitters

A

o Pain – substance P and opioid peptides
o Stress responses – Corticotropin releasing factor
o Food intake – Neuropeptide Y, melanocortin
o Pituitary peptides – vasopressin, oxytocin
o Hypothalamic-releasing peptides

386
Q

Describe the synthesis of acetylcholine

A

Acetyl coenzyme A + choline –> acetylcholine + coenzyme A

Synthesised by choline acetyl transferase enzyme (ChAt)

387
Q

What stores acetylcholine?

A

Stored in synaptic vesicles by vesicular Ach transporter pumps (VaChT)

388
Q

Name the two acetyl receptor types and state where they are found

A

Nicotinic – ionotropic, acts as a channel for positively charged ions, mainly sodium
o N1 – neuromuscular junctions
o N2 – brain, parasympathetic, sympathetic nervous systems

Muscarinic – metabotropic, G-protein coupled receptors
o M1, M3, M5 – excitatory
o M2, M4 – inhibitory

389
Q

Describe acetylcholine in the autonomic nervous system

A

Sympathetic
o Ach preganglionic (nicotinic)
o Noradrenaline/adrenaline post synaptic

Parasympathetic
o Ach pre (nicotinic) and post ganglionic (muscarinic)

390
Q

Describe nicotinic Ach receptors

A
  • Agonist – Nicotine, mimics Ach
  • Ligand gated ion channels – Na, K , Ca
  • Short duration
  • 5 subunits to make a receptor (pentamer)
  • 5 types of subunit – alpha (1-10), beta (2-5), delta, epsilon and gamma
    o Allows for a great diversity of receptors
391
Q

Describe the selectivity of toxins to specific receptor types

A
  • Alpha-bungarotoxin – toxin in the venom of Kraits
  • Binds to the nicotinic Ach receptor
  • Sensitivity to toxin varies with Ach subunit composition
  • Bungarotoxin sensitive – homodimers of a7 or a9
  • Bungarotoxin insensitive – combination of a2 -a6 or b2 -b4
392
Q

Describe muscarinic Ach receptors

A
  • Agonist – Muscarine
  • Inverse agonist – Atropine
  • GPCRs – G-protein coupled receptors
    o 7 transmembrane domains
  • Long duration
  • Excitatory or inhibitory
  • Can indirectly activate ion channels through activation of GPCR
    o Heart M2 receptor activation leads to K channel opening
  • M1-5 – All in the CNS
  • Other tissues –
    o M1 – Secretory
    o M2 – Cardiac
    o M3 – Smooth muscle and secretory
393
Q

Describe myasthenia gravis

A

Increased muscle weakness on activity

Autoimmune disorder

Auto antibodies against extracellular components of NMJ
o	nAchR
o	Muscle-specific kinase (Musk)
o	Lipoprotein-related protein 4 (LRP4)
o	Agrin
394
Q

What are the symptoms of acetylcholinesterase inhibition?

A

SLUDGEM

  • Salivation
  • Lacrimation
  • Urination
  • Defecation
  • Gastrointestinal upset
  • Emesis
  • Miosis
395
Q

Describe short-term plasticity

A
  • Millisecond to second timescale
  • Temporary
  • Generally related to amount of neurotransmitter release
396
Q

Describe synaptic facilitation

A

Paired stimuli – 10ms apart

Second PSP is greater than first

Synaptic Ca2+ facilitates neurotransmitter
o Ca2+ already raised when a second stimuli arrives quickly after the first
o Resulting in more neurotransmitter release

Facilitation decreases as interval increases
o Ca2+ concentration decreases quickly post stimuli
o The longer the interval the lower the Ca2+ concentration

397
Q

Describe synaptic depression

A
  • Train of stimuli, post-synaptic potential decreases with each
  • Caused by depleting of the synaptic vesicle pool
398
Q

What are the basic properties of LTP?

A
  • Co-operativity – crucial number of fibres simultaneously activated
  • Input specificity – synapse must be activated during induction
  • Associativity – induction at concurrently active synapse
  • Hebbs law – cells that fire together wire together
399
Q

Describe the mechanisms underlying LTP

A

Induction of LTP is NMDA (type of glutamate receptor) receptor-dependent

High frequency stimulus – prolonged depolarisation and alleviation of Mg2+ block on NMDA receptors

Sodium and calcium enter cell through NMDA receptor triggering LTP
o Large fast increase of Ca2+
o Kinase activation
o Insertion of additional AMPAR
o Retrograde signalling causes presynaptic changes (later)

Induction can be blocked by Ca2+ chelators

400
Q

Describe long-term synaptic depression

A
  • Involves internalisation of AMPAR
  • Induces dendritic spine growth
  • Occurs in the cerebellum and hippocampus
  • Small and slow increase of Ca2+
  • Phosphatase activation
  • Dephosphorylation of stargazin and endocytosis of AMPAR
401
Q

Describe cereblellar LTD

A
  • Glutamate release from Purkinje fibre activates MGluR
  • Climbing fibre activation (strong) depolarises Purkinje cell
    o Opens voltage gated calcium channels
  • Synergistic activation of PKC (and MAPK)
    o Results in the internalisation of AMPA receptors
  • May be important in motor learning
402
Q

Describe glutamate synthesis

A

Glutamate is a non-essential amino acid that does not cross blood brain barrier
o Requires local synthesis in CNS

Usually in astrocytes as recycling process
o Constant recycling of glutamate dependent on influx of glutamine from outside sources
o Glutamate broken down in astrocyte to form glutamine (by glutamine synthetase)
o Glutamine then passed back into presynaptic neuron

403
Q

Name some glutamate receptor agonists

A

N-methyl-D-aspartate (NMDA)
AMPA
Kainate

404
Q

Describe the two broad types of glutamate receptor

A 
Ionotropic 
o	Non-selective cation channels
o	NDMDA – N-methyl-D-aspartate – Glycine required as co-agonist
o	AMPA
o	Kainate

Metabotropic
o Different receptor subtypes vary in their calcium permeability

405
Q

What is the postsynaptic framework?

A

Scaffold of proteins that mediate postsynaptic response

406
Q

What is the neuronal activity of glutamate?

A
  • Marked increase in cytosolic Ca2+ concentration
  • Functions as a second messenger mediating a wide range of cellular responses
  • Excessive influx or release from intracellular stores can overwhelm regulatory mechanisms
407
Q

Describe calcium homeostasis in a cell

A
  1. Ca2+ and Na+ influx along with K+ efflux in receptor gated ion channels, such as glutamate receptors
  2. Ca2+ efflux via an ATP-requiring ionic pump
  3. Ca2+ influx via voltage gated Ca2+ channels
  4. Ca2+ efflux via Na/Ca2+ exchanger
  5. Additional ionic channels contributing to membrane repolarisation and ionic homeostasis
  6. Ca2+ sequestration (and release) by endoplasmic reticulum
  7. Ca2+ fluxes through the nuclear membrane with potential effects on nucleic acid transcription
  8. Ca2+ sequestration by mitochondria
  9. Intracellular Ca2+ buffering by Ca2+ binding proteins
408
Q

What are the different types of glutamate transporters and where can they be found?

A
  • EAAT1, EAAT2 – astrocytes and microglia
  • EAAT3- cerebral neurons
  • EAAT4 – cerebral neurons
  • EAAT5 – retinal
409
Q

What is excitotoxicity and what can it cause?

A

Excessive influx of Ca2+ can overwhelm cell

o Excitotoxic cell death implicated in Ischaemia, Alzheimer’s, Parkinson’s, Huntingdon’s, ALS
o Characterised by loss of particular groups of neurons
o Often late onset – suggests ageing a factor and accumulation of stresses acting on post mitotic cells

410
Q

What are the two major hypotheses about the relationship between calcium overload and neurotoxicity?

A
  1. Ca2+ load hypothesis
    o Linear relationship between Ca2+ influx and neurotoxicity
  2. Source specific hypothesis
    o Distinct Ca2+ signalling pathways related to influx and neurotoxicity
    o Evidence that distinct influx pathways determine vulnerability
411
Q

Describe the relationship between excitotoxicity and PD

A

Normally balance between striatal activation through NMDA receptors and inhibition through D2 receptors

Depletion of dopamine results in glutamatergic overactivity and change in NMDA subunits

Causes PD secondary glutamate overactivity syndrome

Could be a treatment option
o Many nonselective NMDA antagonists tried in animals
o Show reduction in parkinsonian findings in models
o However – not well tolerated in primates owing to hallucinations and sedation

412
Q

Describe the relationship between excitotoxicity and Alzheimer’s

A

Glutamate may be a major executor of neuronal damage in AD

Amyloid (beta and tau) related to glutamate activation of NMDA receptors enhances production of these factors

NMDA antagonist – Memantine
o Uncompetitive antagonist with improved voltage dependent kinetics and affinity that leads to functional improvement

413
Q

Name the parts of the brachial plexus

A 
Roots
Trunks
Divisions
Cords
Branches
414
Q

Name the terminal branches of the brachial plexus

A 
Musculocutaneous
Axillary
Median
Radial 
Ulnar
415
Q

What is winging of the scapular? What muscle, nerve and nerve roots are involved?

A

Shoulder blade sticks out

Serratus anterior
Long Thoracic nerve
C5, C6, C7

416
Q

What are the main muscles that adduct the arm? Name their nerve supplies

A

Pectoralis major - medial pectoral nerve
Latissimus Dorsi - thoracodorsal nerve
Teres major - lower scapular nerve

417
Q

What are the main muscles that abduct the arm? Name their nerve supplies

A

Deltoid - Axillary nerve (C5/C6)

Supraspinatus (first 15 degrees) - suprascapular nerve (C5, C6)

418
Q

Name the rotator cuff muscles. What nerve roots are they supplied by?

A

Supraspinatus
Infraspinatus
Subscapularis
Teres minor

All innervated by nerve roots C5, C6

419
Q

What muscles are in the anterior compartment of the upper arm? Describe their action and nerve supply

A

Biceps brachii
Coracobrachialis
Brachialis

Flexes arm at elbow (+ shoulder)

Innervated by the musculocutaneous nerve (C5 C6, C7)

420
Q

What muscles are in the posterior compartment of the upper arm? Describe their action and nerve supply

A

Triceps brachii

Extension of arm at elbow

Radial nerve (C5-T1)

421
Q

Whats muscles are in the anterior forearm? Describe their action and nerve supply

A 
Flexor Carpi ulnaris
Palmaris Longus
Flexor carpi radialis
Pronator teres
Flexor digiti superficialis 
Flexor digitorum profundus
Flexor Pollicis longus
Pronator Quadratus

Flexion + adduction of wrist
Pronation of forearm
Flexion of fingers + thumb

Median nerve (C5-T1) except for flexor carpi ulnaris and medial half of FDP (ulnar nerve)

422
Q

Whats muscles are in the posterior forearm? Describe their action and nerve supply

A 
Brachioradialis
Extensor carpi radialis longus and brevis
Extensor digitorum 
Extensor digiti minimi 
Extensor carpi ulnaris 
Anconeus 
Supinator
Abductor pollicis longus 
Extensor pollicis brevis + longus
Extensor indicis proprius

Extension and abduction of wrist
Supination of forearm
Extends fingers

Radial nerve (C5-T1)

423
Q

What are the thenar muscles of the hand? Describe their nerve supply

A

Opponens pollicis
Abductor pollicis
Flexor pollicis brevis

Median nerve (C5-T1)

424
Q

What are the hypothenar muscles of the hand? Describe their nerve supply

A

Opponens digiti minimi
Abductor digiti minimi
Flexor digiti minimi

Ulnar nerve (C8, T1)

425
Q

What is the action of the lumbricals and what is their nerve supply?

A

Flex at the MCP joint and extend at the IP joints

Lateral lumbricals - median nerve
Medial lumbricals - ulnar nerve

426
Q

What is the action of the interosseis and what is their nerve supply?

A

Dorsal interossei - abduct the fingers
Palmar interossei - adduct the fingers

Ulnar nerve (C8, T1)

427
Q

What is the action of adductor pollicis and what is its nerve supply?

A

Adducts the thumb

Ulnar nerve (C8, T1)

428
Q

What dermatome is C5?

A

Over deltoid

429
Q

What dermatome is C6?

A

Index finger

430
Q

What dermatome is C7?

A

Middle finger

431
Q

What dermatome is C8?

A

Little finger

432
Q

What dermatome is T1?

A

Inner arm

433
Q

What dermatome is T2?

A

Apex of axilla

434
Q

What level does the spinal cord end and what does it form?

A

L2 - spinal cord tapers, forming the conus medullaris

435
Q

What is the cauda equina?

A

Spinal nerves that arise from the end of spinal cord bundled together

436
Q

What are the two points of enlargement of the spinal cord?

A

o Cervical enlargement – C4 to T1 – represents the origin of the brachial plexus
o Lumber enlargement – T11 to L1 – represents the origin of the lumbar and sacral plexi

437
Q

Describe the spinal meninges

A

Filum terminale – meninges from this strand of fibrous tissue at end of the spinal cord – attaches to the vertebral bodies of the coccyx and acts as anchor

Dura mater
o Extends from the foramen magnum to the filum terminale
o Spinal nerves pierce dura – dura surrounds nerve root and fuses with the outer connective tissue (the epineurium)

Arachnoid mater
o Distal to the conus medullaris the subarachnoid space continues to form the lumbar cistern
o Accessed during a lumbar puncture

Pia mater
o Fuses with the filum terminale
o Between the nerve roots, the pia mater thickens to from the denticulate ligaments – attach to the arachnoid mater – suspending the spinal cord in the vertebral canal

438
Q

What is the ventriculus terminalis?

A
  • Also known as the fifth ventricle
  • Ependyma lined CSF-filled cavity within the conus medullaris
  • Formed during embryogenesis via canalisation and retrogressive differentiation of caudal spinal cord and regresses completely during early childhood
439
Q

Where do nerve roots exit the vertebral column?

A

Cervical nerve roots exit above the vertebrae

This switches after C7 - C7 comes out between C7 and T1

440
Q

What do the dorsal and ventral rami supply?

A 
o	Posterior (dorsal) rami – supplies nerve fibres to the synovial joints of the vertebral column, deep muscles of the back, and the overlying skin
o	Anterior rami (ventral) – supplies the nerve fibres to much of the remaining area of the body, both motor and sensory
441
Q

What do the ventral and the dorsal horns of the spinal cord contain?

A
  • Ventral (anterior) horns – motor neurons

- Dorsal (posterior) horns – sensory neurons

442
Q

What are Rexed Laminae?

A
  • Cells grouped by their function and location rather than simply by their location
  • Laminas 1, 2, 3, 4 and 5 – predominantly involved in interpreting and relaying sensory information from the brain
  • Laminas 7,8 and 9 – involved primarily in executing movement and controlling the functions of organs
  • Laminae 9 – contains the alpha, beta and gamma motor neurons
443
Q

Describe the three neuron chain of ascending tracts

A
  • First order neurons – cell bodies in dorsal root ganglia
  • Second order neurons – cells bodies in the grey matter of the brain stem or spinal cord – gives rise to axons that cross the midline, before ascending to the thalamus
  • Third order neurons – located in the ventral posterior (VP) nucleus of the thalamus – project to the primary somatosensory cortex (via the posterior limb of the internal capsule)
444
Q

Describe the path of the dorsal column

A
  • Contains two fasciculi
    o Fasciculus gracilis – closer to the midline, present at all cord levels. Transmits sensory information from T6 and below
    o Fasciculus cuneatus – wedge shaped, lateral to gracilis. Only present in the upper half of the cord. Contains sensory fibres from above T6
  • First order neurons enter dorsal column without crossing the midline and terminate in the dorsal column nuclei (gracile and cuneate nuclei) in the medulla
  • Second order neurons arch anteriorly and medially through the medulla – internal arcuate fibres
  • All second order neurons cross the midline together – in the great sensory decussation of the medulla
  • Ascend to the thalamus as the medial lemniscus
  • Third order neurons – thalamus to the primary somatosensory cortex
445
Q

What fibres does the dorsal column contain?

A

Alpha fibres - large myelinated axons

446
Q

What fibres does the spinothalamic tract contain?

A

Unmyelinated c-fibres and thinly myelinated A-delta fibres

447
Q

Describe the path of the spinothalamic tract

A
  • First order neurons – central processes enter the spinal cord where they synapse on second order neurons in the dorsal horn
  • Second order neurons – axons cross the midline via the ventral white commissure. Ascend in the anterolateral spinal cord and pass through the brainstem as the spinal lemniscus. Terminates in the thalamus
  • Third order neurons – project to the primary somatosensory cortex
448
Q

What are the spinocerebellar tracts and what are they responsible for?

A
  • Posterior (Dorsal) spinocerebellar – carries proprioceptive information from lower limbs to ipsilateral cerebellum
  • Cuneocerebellar tract – carries proprioceptive information from the upper limbs to the ipsilateral cerebellum
  • Anterior spinocerebellar tract – carries proprioceptive information from the lower limbs. The fibres decussate twice – terminate in the ipsilateral cerebellum
  • Rostral spinocerebellar tract – carries proprioceptive information from the upper limbs to the ipsilateral cerebellum
449
Q

Where do fibres of the corticospinal tract arise?

A
  • 2/3 of fibres – arise from the primary motor and premotor cortex
  • 1/3 of fibres – arise from the primary somatosensory cortex and synapse in the dorsal horn – filters out barrage of sensory information created by complex movements
450
Q

Describe the course of the corticopsinal tract

A

1) Originates in cerebral cortex entering the subcortical white matter, passing through the posterior limb of the internal capsule to reach the crus cerebri in the anterior midbrain
2) Through basilar pons to enter medulla where they occupy the anterior midline as the pyramids
3) At the lower border of the medulla – 75-90% of fibres decussate
4) Continues as the lateral corticospinal tract – supplies the distal limb musculature
5) Uncrossed fibres are a direct continuation of the medullary pyramids – continue as the anterior corticospinal tract. Many of these fibres eventually decussate and chiefly innervate the proximal and axial musculature

451
Q

Describe the corticobulbar tract

A
  • Arises in the cerebral cortex (mainly from the face and tongue areas of the primary motor and premotor cortexes) and projects to the brainstem
  • Accompany the corticospinal tract as far as the brainstem
  • Projects directly to four motor cranial nerve nuclei
  • Innervates muscles involved with –
    o Chewing
    o Facial expression
    o Mediate speech, swallowing and the efferent limb of the gag reflex
    o Control the toing
452
Q

Does damage to one side of the brain affect the corticobulbar tract?

A
  • Most of the cranial nerve nuclei receive projections from both cerebral hemispheres – damage on one side of the brain does not cause contralateral bulbar weakness
    o Exception – cortical projections controlling the tongue and lower part of the jaw – arise mainly from the opposite motor cortex
453
Q

What are the extrapyramidal tracts involved in?

A
  • Involuntary and autonomic control of all musculature

- Originate in brainstem, carrying motor fibres to the spinal cord

454
Q

What are the vestibulospinal tracts?

A

o Remain ipsilateral
o Arises from the vestibular nuclei
o Controls balance and posture

455
Q

What are the reticulospinal tracts?

A

o Medial – arises from pons. Facilitates voluntary movements and increases muscle tone
o Lateral – arises from the medulla. Inhibits voluntary movements and decreases muscle
o Remains ipsilateral

456
Q

What are the rubrospinal tracts?

A

o Originate from the red nucleus
o Fibres decussate as they emerge
o Exact function unclear – play a role in the fine control of hand movements

457
Q

What are the tectospinal tracts?

A

o Begins at the superior colliculus of the midbrain
o Fibres decussate
o Receives inputs from the optic nerves
o Coordinates movements of the head in relation to visual stimuli

458
Q

Describe stretch reflexes

A
  • Monosynaptic reflex
  • Important postural reflex
  • Basis of tendon jerk
459
Q

What are muscle spindles sensitive to?

A

sensitive to rate of change of length of muscle fibres (short sharp stretch is a better stimulus)

460
Q

What is the difference between intrafusal and extrafusal muscle fibres?

A
  • Intrafusal – muscle fibres inside the spindle

- Extrafusal – muscle fibres making up the bulk of the muscle

461
Q

Describe the flexor reflex?

A
  • Polysynaptic reflex

- Withdrawal of a limb in response to pain (protective)

Clinical Neurology (3 decks)

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