Robyn Neuro Flashcards
1
Q
What are the four neurone morphologies?
A
- Multipolar neuron
- Bipolar neuron
- Pseudo-unipolar neuron
- Unipolar neuron
2
Q
Where can bipolar neurons be found?
A
In the retina
3
Q
Where can unipolar neurons be found?
A
Dorsal root ganglia
4
Q
Where can pseudo-unipolar neurons be found?
A
Dorsal root ganglia
5
Q
Where can multipolar neurons be found?
A
In the brain for example the hippocampus
6
Q
What are the types of glial cell?
A
- Astrocytes
- Oligodendrocytes
- Glioblasts
7
Q
What are the functions of astrocytes?
A
- Create the brain environment, build up the micro-architecture of the brain parenchyma,
- Maintain brain homeostasis, store and distribute energy substrates,
- Control the development of neural cells
- Synaptogenesis and synaptic maintenance
- Brain defence.
8
Q
What are the differences between fibrous and protoplasmic astrocytes?
A
Fibrous: – White matter (myelinated axons) – Many fibrils in cytoplasm Protoplasmic: – Found in Grey matter only – Shorter, stouter processes – Few cytoplasmic fibrils and organelles
9
Q
What are the functions of oligodendrocytes?
A
Myelinate axons in the CNS, can myelinate more than one axon at a time
10
Q
Describe the morphology and functions of microglia?
A
Short spiky processes
• Wide distribution
• Derived from circulating monocytes
• Phagocytosis similar to macrophages
• Major inflammatory cell type in the brain
• Respond to pathogens and injury by becoming ‘activated’ –change morphology, proliferate
and migrate to the site of infection/injury.
• They phagocytose and destroy pathogens as well as remove damaged cells.
11
Q
Describe the morphology and functions of ependymal cells?
A
They are epithelia lining ventricles and spinal canal
ciliated, cuboidal/columnar cover capaillaries
‘choroid plexus’. Choroid plexus secretes the CSF
12
Q
Which part of the brain has a high density of neurones?
A
The cerebellum which has 40% of the brain’s neurones despite its size
13
Q
What does the cerebellum do?
A
- Muscle tone
- Co-ordination
- Motor error – checking
- Learning
14
Q
Name the main lobes of the cerebrum
A
Frontal, Parietal, Occipital, Temporal
15
Q
What is the function of the frontal lobe?
A
Personality, higher thought
16
Q
Name the main sulci of the brain
A
The central sulcus, the parieto occipital sulcus, lateral sulcus
17
Q
Name the main gyri of the brain
A
The pre central gyrus- primary motor cortex is here
The post central gyrus- primary somatosensory cortex is here
The superior temoral gyrus- has some role in sound processing
18
Q
What are the planes of the view of the brain?
A
Coronal- shows the front
Sagital- shows the side
Horizontal- shows the horizontal view
19
Q
What is a commisural fibre?
A
It connects the two hemispheres of the brain- the corpus callosum is the largest example of one
20
Q
What are the four divisions of the brain?
A
The cerebrum, cerebellum, brainstem and diencephalon
21
Q
What makes up the brainstem?
A
Composed of:
- Medulla oblongata
- Pons
- Midbrain
22
Q
What is decussation?
A
The action of crossing
23
Q
What do the pyramidal tracts carry?
A
Motor fibres
24
Q
What are the major features of the medulla oblongata?
A
Fibre tracts - Nuclei CVS, respiration - Olives Cerebellum - Nerve roots
25
What are the major features of the pons?
- Connects to cerebellum via peduncles
- Respiratory centres
- Fibre tracts
26
What are the major features of the cerebellum?
- Folia- leaves
- Layers
- Deep nuclei
- White matter
27
What are the main features of the midbrain?
- Cerebral peduncles
- Tectum (roof of midbrain)
Superior and inferior colliculi
Visual (superior) and auditory (inferior) reflexes
- Substantia nigra-black due to melanin byproduct
- Nucleus ruber-motor coordination-pinky red due to
haemoglobin and ferritin
Substantia nigra
28
What does the reticular formation do?
Reticular activating system
Circadian rhythm
Alertness
Emotion
29
What are the main features of the diencephalon?
- Part of forebrain
- Links midbrain and cerebrum
- Contains
Thalamus
Hypothalamus
Pineal
30
What does the thalamus do?
Thalamus: processing and relay centre
- All special senses expect smell
- Synaesthesia- cross over of vision and hearing
- Motor role
- Arousal, emotion
- Higher functions
31
What does the pineal gland do?
Pineal:
- Endocrine organ
- Melatonin and serotonin
Circadian rhythms
32
What are all the lobes of the brain?
- Frontal
- Parietal
- Occipital
- Temporal
- Central (insula)
- Limbic: non-medial surface
33
Where is Brocca's area?
On the frontal lobe
34
Where is Wernicke's area?
On the posterior temporal lobe
35
Describe the lateralisation of the brain
```
• Left hemisphere
– Speech
– Calculation
– Analysis
• Right hemisphere
– Spatial
– Conceptual
– Artistic
```
36
What are the basal ganglia?
```
• Deep within hemispheres
• Movement
– Parkinson’s
– Huntington’s
• Caudate and putamen (striatum)
• Globus pallidus
• Subthalamic nucleus
• Substantia nigra (part of the midbrain)
```
37
What are the parts of the limbic system?
* Memory, emotions
* Limbic lobe (green)
* Hippocampus and amygdala
* Thalamus, hypothalamus
* Reticular formation
* Memory / emotion / motivation
38
What are the different types of central fibre tract?
```
• Association fibres
– Link areas within a hemisphere
• Commissural fibres
– Connect between hemispheres
• Projection fibres
– Link to non-cortical areas
```
39
What is rostral?
Towards the face/ more anterior in the brain (think rostral and nostril)
40
What is caudal?
Caudal refers to something more posterior in the brain or down the spinal cord- towards the tail end
41
What is dorsal?
That refers to more superior in the brain
42
What is ventral?
That refers to more inferior in the brain
43
What is ipsilateral?
On the same side
44
What is contralateral?
On the opposite side
45
What are the three nervous systems?
- Central nervous system (CNS)
- Peripheral nervous system (PNS)
- Enteric nervous system (the gastrointestinal tract is enteric)
46
What is the central nervous system?
- Central nervous system comprises the brain and spinal cord
| - Everything else is the peripheral nervous system
47
What is the peripheral nervous system?
- The nerves and cell bodies to/from brain and spinal cord
- Some PNS cells lies in the CNS e.g neurones innervating muscle – motoneurons
- 43 pairs of peripheral nerves enter/exit the brain and spinal cord
- The cranial and spinal nerves
Anything outside the brain and spinal cord
Motor neurones power cells, they are considered peripheral
48
What is the structure of peripheral nerves?
```
- Nerves are bundles of individual neuron
axons
- No neural cell bodies
- Most are mixed: both sensory axons and
motor axons present
Some are myelinated by Schwann cells
```
49
What is cranial nerve I?
The olfactory nerve
50
What does the olfactory nerve do?
Smell
51
What is cranial nerve II?
The optic nerve
52
What does the optic nerve do?
Carries visual information from the retina to the primary visual cortex in the occipital lobe
53
What is cranial nerve III?
The occulomotor nerve
54
What does the occulomotor nerve do?
It moves the eye
55
What is cranial nerve IV?
The trochlear nerve
56
What does the trochlear nerve do?
It innervates the superior oblique muscle which rotates the eye
57
What is cranial nerve V?
The trigeminal
58
What are the three parts of the trigeminal nerve?
V1- The opthalmic branch
V2- The maxillary branch
V3- The mandibular branch
59
What does the trigeminal nerve do?
Face sensation and chewing
60
What is cranial nerve VI?
The abducens nerve
61
What dos the abducens nerve do?
It abducts the eye, innervates the lateral rectus muscle
62
What is cranial nerve VII?
The facial nerve
63
What does the facial nerve do?
Muscles of the face, scalp and side of neck
64
What is cranial nerve VIII?
The vestibulocochlear nerve
65
What does the vestibulocochlear nerve do?
Hearing and balance
66
What is cranial nerve IX?
The glossopharyngeal nerve
67
What does the glossopharyngeal nerve do?
Sensorry for the pharynx, tonsils, middle ear and posterior 1/3 of the tongue
68
What is cranial nerve X?
The vagus nerve
69
What does the vagus nerve do?
Lots- the innervation of respiratory, cardiovascular and digestive system
70
What is cranial nerve XI?
The accessory nerve
71
What does the accessory nerve do?
The trapezius muscle and a muscle in the neck
72
What is cranial nerve XII?
The hypoglossal nerve
73
What does the hypoglossal nerve do?
It innervates most of the internal and external muscles of the tongue
74
What are the two divisions of the nervous system?
Somatic and autonomic
75
What is the somatic nervous system?
The motor neurones go straight to the muscle (basically what you can control)
76
What is the autonomic nervous system?
Motor axons connect (synapse) with another cell in a ganglion, this cell
innervates muscle or gland
Nerves and reflexes not under your control
77
What are the two divisions of the autonomic nervous system?
The sympathetic and parasympathetic nervous systems
78
What does the sympathetic nervous system do?
Fight or flight responses
79
What does the parasympathetic nervous system do?
Rest and digest responses
80
What is the myelination like in the autonomic nervous system?
Pre- ganglionic axons myelinated
| Post-ganglionic axons are not
81
What are the neurotransmitters of the autonomic nervous system?
Preganglionic neurotransmitter: Ach
| Postganglionic neurotransmitter: noradrenaline
82
What is the mechanism of the formation of the neural tube?
Neural grove gradually deepens as the neural folds
become elevated
The folds meet and coalesce in the middle line and
convert the groove into the closed neural tube
The ectodermal wall of the tube forms the rudiment of
the nervous system. The centre of the tube is the neural
canal
83
After how many days does the neural plate go down and he neural folds go up?
20 days
84
What are primary brain vesicles?
Vesicles are fluid-filled swellings at the rostral end of the neural tube
Early vesicle expands and grow differently
Each vesicle is a swelling of neural tube
(prosencephalon, mesencephalon, rhombencephalon)
85
What are secondary brain vesicles?
Flexions and out-pocketing’s continue
The pockets are called flexions
Optic vesicle turns into eyes
Telencephalon turns into cerebrum
86
What would a transverse section of the spinal cord show?
White matter on the outside, grey matter on the inside
Dorsal nerve roots= afferent fibres
Ventral nerve roots= efferent fibres
87
What is an afferent fibre?
It carries sensory information towards the brain and CNS
88
What is an efferent fibre?
It carries motor information away from the brain and CNS- to an effector
89
Which pathways run up and down the spinal cord?
Ascending and descending
| pathways
90
What are the three layers of the meningies?
Outermost to innermost
Dura mater
Arachnoid mater
Pia mater
91
What are the two layers of the dura mater?
Endosteal- outside layer
| Meningeal- inside layer
92
What is CSF?
Cerebrospinal fluid- it bathes the brain and is in teh central spinal canal, it is within the ventricles of the brain
93
What forms the CSF?
The choroid plexus in the brain
94
What are the functions of CSF?
Provides the brain with nutrients and cushions it
95
What absorbs the CSF once it has been used?
The arachnoid granulations, in the layer of arachnoid mater
96
What is the blood brain barrier?
- A semipermeable membrane separating the blood from the cerebrospinal fluid, and
constituting a barrier to the passage of cells, particles, and large molecules
97
What are some key parts of the blood brain barrier?
Astrocytes
Capillaries in brain have very tight gap junctions
Stops particles getting into brain- therefore difficult to produce drugs for the brain
98
What happens if the CSF doesn't flow and builds up?
Hydrocephalus may occur
99
What happens if the neural tube doesn't form?
Spina bifida- if the neural tube doesn't close
Anencephaly- The abscence of a major portion of the brain
Folic acid helps prevent neura tube deformations
100
What are the two major components of the somatic sensory system?
Two major input components:
– Mechanical stimuli (light touch, vibration, pressure and cutaneous tension)
– Painful stimuli and temperature
101
What does somatic sensory inputs and interpretation allow you to do?
– To identify the shape and textures of objects
– To monitor the internal and external forces acting on the body
– To detect potentially harmful circumstances
– And, therefore, to have a sense of ourselves within our environment and so plan our
actions accordingly
102
What are the various types of sensory receptors?
Encapsulated nerve endings-
Pacinian: located deeper
in the skin- does deep pressure
Meissner: on the surface of skin- does light touch and texture
Ruffini: Subcuatneous tissue, joints- does heavy touch, skin stretch, joint movement
Unencapsulated nerve endings-
Merkel: superficial skin- light tough and texture
Free Nerve Endings: Widespread in epithelia- pain, hot, cold
103
Which two main routes carry the sensory information get to the brain?
– The Medial Lemniscal tracts carry mechanoreceptive
and proprioceptive signals to the thalamus
– The Spinothalamic tract carries pain and
temperature signals to the thalamus
104
Which three neurones does sensory information pass through to reach higher centres?
– First-order neurons detect the stimulus and transmit
to spinal cord in Dorsal root ganglia
– Second-order neurons relay the signal to the
thalamus, the “gateway” to the cortex
– Third-order carry the signal from the thalamus to the
cortex
105
Are the second order neurones commisural?
Yes they are, axons of the second order neurons cross the midline in the ventral white commissure to reach opposite side
106
How is the medial lemniscal system organised?
– 1st order axons from the upper body follow the
lateral (red) pathway and synapse on 2nd order
neurons in the cuneate nucleus
– 1st order axons from the lower body (below vertebra
T6) follow the more medial (purple) pathway as
closer to the midline and synapse on neurons in the
gracile nucleus
– Together these are known as the dorsal column
nuclei
• 2nd order axons cross the midline and ascend in the medial
lemniscus.
• Finally, 3rd order axons again reverse the topology so that lower body axons synapse on
more medial cortical neurons, whereas upper body axons ‘map’ to the lateral cortex
107
What is a dermatome?`
• Each sensory ganglion innervates a specific region of skin
| called a dermatome
108
What is a somatosensory homunculus?
It is where there is a distorted amount of processing to the size of the organ- the diagrams with the huge lips have a look
(The area of cortex dedicated to each area of the body is proportional to the density of
innervation in that area (and hence its behavioural significance) not to the physical size of
the area)
109
What are reflexes?
Reflexes are simple, local circuits in the spinal cord usually involving sensory input and motor
output
110
What is the difference between monosynaptic and polysynaptic reflexes?
Reflexes may involve a single synapse between sensory and motor neuron (ie monosynaptic;
e.g. stretch reflex), or may involve interneurons (ie polysynaptic; e.g. flexor reflex)
111
What are some features of spinal reflexes?
They require stimulation
They are quick
Involuntary and automatic
Stereotyped- occur in the same way each time
112
What is an example of a monosynaptic reflex?
The knee jerk reflex
113
What is a golgi tendon organ?
• The GTO is another kind of proprioceptor
• GTOs detect muscle tension due to muscle contraction, not muscle
stretch (which is detected by muscle spindles)
114
What is the golgi tendon reflex?
Thus, the Golgi Tendon Reflex is a negative feedback circuit that
regulates muscle tension and protects the muscle (and tendon) from
damage when large forces are generated.
115
What is the flexor (withdrawal) reflex?
• Flexor reflex is a quick contraction of flexor muscles to withdraw a limb from an
injurious stimulus (e.g. heat or cut)
• It results from the activation of nociceptive sensory receptors (noci- = hurt, e.g.
noxious) or nociceptors
• Despite speed of response, this is a polysynaptic reflex
116
What is Robyn?
Fit as fuck
117
What is the specificity theory of pain?
Specificity theory holds that pain is a distinct sensation, detected and transmitted by specific
receptors and pathways to distinct “pain areas” of the brain.
118
What is the convergence theory of pain?
Convergence theory suggests that pain is an integrated, plastic state represented by a
pattern of convergent somatosensory activity within a distributed network (a so-called
‘neuromatrix’).
119
What are nociceptors?
Nociceptors respond specifically to pain and are a subset of afferents with free nerve endings
120
What are the two catagories of pain?
Fast or ‘first’ pain; sharp and immediate; can be mimicked by direct stimulation of A fibre nociceptors
Slow or ‘second’; more delayed, diffuse and longer-lasting; mimicked by stimulation
of C fibre nociceptors
121
What is the difference between A fibres and C fibres in pain?
A- can be A alpha or A beta and they proprioceptive or mechanoceptive- they give the pain sensation
C- These are slower and give pain such as that from bruising
122
What are the two components of central pain pathways?
Sensory discriminative:
• signals location, intensity and
type of stimulus how intense
– Affective-motivational:
• signals ‘unpleasantness’, and
enables autonomic activation,
classic flight or fight response
123
What are the locations of free nerve endings?
Widespread throughout epithelia and connective tissues
124
What is hyperalgesia?
Result of lowered nociceptor thresholds which heightens pain response
125
What is somatotopy?
Somatotopy is the point-for-point correspondence of an area of the body to a specific point on the central nervous system. Typically, the area of the body corresponds to a point on the primary somatosensory cortex
126
Do motor neurones exhibit somatotopy?
Yes they do
127
Where do upper motor neurones and lower motor neurones synapse?
Upper motor neurons always synapse on lower motor neurons (or their
interneuron circuitary), whereas lower motor neurons always synapse directly on muscle
fibres
128
What do upper motor neurones of the motor cortex do?
– Initiate complex voluntary movements
– Project mainly contralaterally via the corticospinal tract primarily to muscles
involved in precise limb movements, particularly those of the hands in humans
– (Also, project via the corticobulbar tract to the hypoglossal nucleus in the
brainstem, which controls movements of the tongue - important for speech in
humans)
129
What do upper motor neurones of the brainstem do?
– More concerned with the maintenance of posture and balance
– Located in several nuclei including
• Reticular formation
• Vestibular nucleus (vestibular co-ordination)
• Superior colliculus (visual co-ordination)
– Project ipsilaterally mainly to lower motor neurons controlling axial muscles
concerned with maintaining posture
130
Which are the other main areas of the brain involved in motor control? (other than the motor cortex)
The basal ganglia and the cerebellum
131
How do the basal ganglia and cerebellum influence movement?
These structures influence movement indirectly by regulating the function of upper motor
neurons
132
How does the basal ganglia initiate movement?
1. With no initiating cortical input, the Globus Pallidus tonically inhibits the VLo due to tonic
activation from the Caudate/Putamen (=Striatum)
2. Input from many cortical regions converges on the striatum.
3. When activated by this input, the Striatum inhibits the
inhibitory activity of the GP, (shutting down inhibition that
was there) releasing the VLo to activate Area 6 (specifically
the motor cortex) and initiate movement. Input from various
parts of the cortex including the prefrontal, sensory etc that
sets up the initiation
133
What are the main muscle influencing tracts?
Vestibulospinal and Reticulospinal
134
What is the motor loop?
• The motor cortex also connects to the basal ganglia,
which in turn feedback to the premotor area (Area 6) via
the ventrolateral complex of the thalamus (VLo) to
control the initiation of movement.
• This is known as a ‘Motor Loop’
135
What is the function of the cerebellum?
Primary function is to detect and correct differences
between the intended movement and the actual
movement - the so-called motor error.
136
Why does Huntington's and Parkinson's occur?
Huntington’s chorea (and Parkinson’s disease) results when ganglia that normally inhibit
movement initiation degenerate
137
What does motor neurone disease affect?
Motor neuron disease can affect either upper or lower motor neurons
138
What is postural control?
Postural control is integrated with movement
Postural control is defined as the act of maintaining, achieving or restoring a state of balance during any posture or activity.
139
What was Ancient Greece view of the brain?
Clear correlation between structure and function
- Hands, feet etc
So what does the head do?
- Holds the senses? Eyes, nose, ears, tongue
Therefore: brain = organ of sensation
Hippocrates (460-370 BC) – Brain = sensation + intelligence
Aristotle (384-322 BC) – Brain = a Radiator
140
What was the Roman empires view of the brain?
```
Galen:
- Cerebrum = squidgy
- Cerebellum = hard
Form = function’ ergo
- Cerebrum = sensations (memories)
- Cerebellum = commands muscles
This is more-or-less correct
```
141
Hypothesis: Nerves as wires
Galen - ventricles hollow – therefore nerves transmit humors to limbs etc.
Galvani, du Bois-Reymond – muscles twitch when electrically stimulated.
Bell, Magendie – cut dorsal and ventral roots - ventral - paralysis
Magendie – nerves mixtures of wires
142
does the brain have different functional domains?
Flourens – regional ablation in birds - - cerebellum controls movement
Different cerebral regions control different functions.
Fritsch, Hitzig (1870) – electrical stimulation in dogs. Ferrer – monkeys
Munk (1878) – ablation of occipital lobe (vision)
In addition – Schwann proposed cell theory
(1838)
143
What did we know by the end of the 19th century?
- The brain communicates with the body electrically via nerves
- The brain has different identifiable parts with different functions
- The brain operates according to the law of nature
- The neuron is the basic functional unit
But how is all this achieved?
20th century neuroscience used model organisms to make massive advances
144
Why is Squid used as a model organism?
J Z Young- proposed the squids giant axon as a model
• Large diameter <1mm
• “Easy” dissection and support
• External and internal perfusion with varying salines
• Allowed determination of ion flows in action potential
Hogdkin, Huxley and Katz used this to measure the action potential
145
Why is Caenorhabditis elegans (C. elegans) used as a model organism?
```
Fully mapped
– Genome
– Nervous system
Model system for developmental cell death
– Apoptosis
Genetic regulation behaviours
```
146
Why is Flies - Drosophila melanogaster used as a model organism?
e.g. identification of genes regulating
– nervous system development
role of pax-6 in eye development / evolution
homologous
behavioural phenotypes
147
Why is frogs used as a model organism?
• Galvani electrical stimulation
* Harrison- how axons grow
* Sperry- how nerves pathfind
* Helmholtz- nerve conduction velocity
* Katz and Miledi- Ca2+ and release
Looking at the eye
148
Why are Birds used as a model organism for development?
```
Birds- development
• Gallus domesticus
• Allows “easy” embryonic manipulation and study
• Transplantation
• Nerve growth factor
```
Viktor Hamburger
Rita levi-montalcini
Nichole Le Douarin
149
Why are bird used as a model organism learning?
Birds- learning
Learning
- Imprinting- Konrad Lorenz
- Passive avoidance learning- Steven Rose
Lecturers notes:
Lorenz – studied imprinting – that is, in some birds (the ones that leave their nest early) they bond with the first moving object they see
Rose used chicks to look at the biochemical changes involved in so-called passive avoidance learning – avoiding a particular response that leads to an adverse stimuli. This is an example of a complex behaviour being able to be investigated at the cellular and biochemical level by using the correct model
Embryo development
How nerve develop
Can move tissue, see effects
‘chick quail transplantation into a normal chick
150
Why is Mammals and non-human primates used as a model organism?
• Hitzig and Fritsch - mapped motor cortex. Dogs
• Sherrington
• reflexes, motor control, localisation. Cats, dogs, apes
• Key Point: Reflexes aren’t just from arcs but need integrated action
• Defined synapse
- Loewi – chemical neurotransmission. Dogs
– Vagustoff (released when the vagus is stimulated, slows the heart.)
• Dale - release ACh from motor nerves. Dogs, cats, frogs
• “Dale’s principle”
• Individual nerves release a single neurotransmitter?
Key discovery: Synapses signal chemically
At all the axonal branches of a neurone, there is release of the same transmitter substance or substances
151
Using model organisms what was Langley's research? what was Lashley's research?
Langley:
Named the autonomic nervous system
Formulated (chemical) receptor theory
Cats, dogs, rabbits
Lashley:
searched for the engram using e.g. rats in mazes
• Ablation studies
Key point: memory is distributed
152
What experiments on the brain did rats undergo?
After specific training – eg searching for food – Different sections of rats brains are lesioned before or after training
Increasing tissue removal degraded memory – but the effect was not location specific.
BUT some location specific memories likely to exist
153
How were Mammals used for researching learning?
```
- Pavlovian learning
Conditioned responses
Pair food with bell
Then bell alone elicits drooling
Key point: neutral signal BEFORE a reflex
```
- Skinner
Operant conditioning
Animal performs task with + or - reinforcement
Key point: reinforcement AFTER a behavior
154
Which animals were used for vision research and how?
- Cat and monkey brain
- Receptive fields
- Visual processing
- Kuffler
- Hubel
- Weisel
155
What research were Mice transgenics used in?
- Molecular dissection of behaviour and diseases
- E.g feedng/reward behaviours in dopamine-deficient mice
- E.g developmental abnormalities like double cortex
- Richard Palmiter
156
Why were Non-Human primates used and how?
* Similarity to human brain
* 1875 - Richard Caton records electrical activity from animal brain inspires…
* Berger to develop human EEG (1924)
157
What are the applications for using animal models in research?
```
Immense knowledge gained
Human pathology e.g.
– schizophrenia
– Alzheimer’s
– Parkinson’s
Treatments e.g.
– epilepsy
– Parkinson’s disease
– cochlear and retinal implants
```
158
State early development of the brain
- Primary brain vesicles and flexures
- 6 weeks- more flexures and swellings
Development of brain begin with neural tube
Get swelling at head end and out growths
Tube starts to twist and bend which eventually swell more, undergo growth to give brain
159
Describe the development of brain at 10 week and 3, 5, 7 and 9 months
* 10w – cerebral expansion and commissures.
* 3m – basic structures established- Lots of cell growth , connections, glia etc being produced
* 5m – CNS myelination begins.
* 7m – lobed cerebrum.
* 9m – gyri (ridge) and sulci.(furrow)- twist and turns
Large increase in brain weight up to 3 years
There is a lot more dev after birth
160
How and when does myelin form?
• Myelination proceeds PNS/spinal cord/brain
• Composition changes
– Galactolipids
– Protein components
• Begins ~5th month in humans; 10 days postnatal in rat
• At peak, oligos produce 3x ‘body weight’ per day
• Most over by 2 years, some in late teens (neocortex)
161
What are the critical periods in brain development of foetus and why?
* Rubella – German measles
* Abnormalities dependent on time of infection.
* 6th week - eye malformations – e.g. cataract.
* 9th week - deafness – organ of Corti.
* 5th to 10th weeks - cardiac malformations.
* CNS disorders in 2nd trimester.
* Risk falls after 16 weeks.
162
What are the symptoms of Foetal alcohol syndrome?
```
• Alcohol crosses placenta.
• Foetus doesn’t clear alcohol well.
Foetal levels higher.
• Facial abnormalities
• Microcephaly
• Loss of cells
• Loss fibres e.g. callosal agenesis
• Disturbed migration
• Irritability
• Motor and intellectual impairment
```
163
Effects of drugs of abuse on developing foetus
```
• Opiates – neonatal withdrawal
• Cocaine – hypoxia, abortion, withdrawal, cognition
• Rhesus monkey studies
• Ecstasy
• Long term effects on hippocampus
• Other effects certain
• Cannabis
• Long term cognitive effects
Cocaine- disturb how layer of the brain form- they don’t form properly
- Reduced of layers in brain can be seen
```
164
Describe the maturation of axon conduction velocity
* Speed of conduction with myelination
* Neonate peripheral nerve ~ 20 - 25m/s
* 1 – 6m 32 – 50m/s
* 6 – 12m 33 – 60m/s
* 12 – 24m 40 – 60m/s
165
Describe development of sensation
• Royal Coll. Obs. Gynae. 1997 and 2010 reviews.
• Somatosensory input e.g. pain, requires connection of receptors, sensory neurons, thalamus and cortex.
Pain
Abortion- when do we start to perceive pain?
Pain is not real, it’s a contract of the brain
Need receptors in peripheral nerves to transmit signals to CNS then thalamus then rest of body- will start to feel the pain
Leads to problem the we don’t know if foetus will feel the pain
166
State example of when different senses and reflexes start to develop
(may have to go in own flash card deck)
* Innervation of dermal skin from 28 weeks / subdermal from 6 - 8 weeks
* DRG connection to spinal cord from 8 weeks. Non - noxious.
* C – fibre (noxious stimuli) connection from 19+ weeks.
* Reflex response to noxious stimuli in 23 week preterm infants.
* Facial responses to heel lancing from 28 weeks.
* Organised thalamus forms from 8+ weeks.
* Retinal inputs arrive at 14 – 16 weeks.
* Myelination from 25 weeks.
* Connections from the thalamus to cortex from 24 weeks. (Sub-plate 12+)
* Evoked potentials in the cortex from 29 weeks (RCOG) or earlier (26 weeks e.g. Taylor et al 1996).
* Recent imaging studies suggest 24 week cortical responses.
167
Explain development of Taste and smell
– Well developed at birth.
– Differentiate mother / non-mother breast pads. Can recognise own mother
– Bottle-fed prefer any lactating female.
What about other senses? motor activity?
Taste and smell – very well developed at birth
Breast pads – can smell there own mum’s pads
168
Explain the development of hearing
• Hearing
– Responsive at birth. But can they understand it?
– Excellent discriminators of language sounds.
– Locate sounds from 3 days. Engineering wise a difficult problem, good we are able to do this at three days old
Hearing
They can respond at birth – whether they understand any of it is unclear
Are they primed for language?
Sound location at 3 days. This is a difficult problem – but good for survival
169
Explain the development of vision
• Eyes open and sensitive from 7 months.
• Vision least well developed at birth.
• Retinal cells sparse and not mature.
• Optic nerves not myelinated.
• Vision blurred – sharper by 6 months.
– Development of ocular dominance columns
• Colour vision develops – good at 2 months. Retina gets matured cones
170
Describe Motor development
* Spontaneous muscle twitches
* Writhing from E28 – 32.
* Increases to birth.
171
Postnatal reflexes
Moro (startle) reflex, stepping, palmar grasp, swimming, Babinski reflex, rooting, sucking
172
Describe the Moro (startle) reflex
– Baby supine – remove head support.
– Trunk extension.
– Cycle of limb extension (abduction - from midline).
– And limb flexion (adduction - to midline).
– Goes 3+ months
173
Describe the Stepping reflex
– Hold up, feet onto surface.
| – Goes 6 weeks
174
Describe the Palmar grasp reflex
– May support own weight.
– Goes by 3-4 months
– Development of inhibition
175
Describe the swimming reflex
– Not all babies
| – May swallow! Goes by 4-6 month
176
Describe the Babinski reflex
```
sign indication if damage in tracts of connections that inhibit toe fanning
– Neonates fan toes when sole stroked
– Adult curl toes
– Descending motor tract damage
– fan
```
Babinski reflexes get lost
Sign – is indicative of damage
You may damage inhibitory pathways that regulate the reflex and effectively suppress the fanning
177
Describe the rooting reflex
– stroke cheek
– nipple seeking
– goes 4-7m
Rooting – Baby will automatically turn their head towards stimulus and make sucking motions
178
Describe the sucking reflex
– stroke lips
| – stroke cheek- will turn towards and start sucking
179
What Co-ordinated responses are there ?
• Significant development post-birth e.g. reaching
– Reaching begins about 5th month
– Around 8-9m attain object
– By 2yr show adult motor patterns
• Significant development post birth e.g language
• Brain regions differ from adults
180
What is Myelin and its composition?
* Lipid-rich, living insulating sheath
* 50% dry weight of white matter
* Synthesised by non-neuronal cells
* Conduction velocity of action potential
* Loss of myelin produces profound neurological disorders
* Myelin may alter in learning and memory
Myelin only surrounds some axons
181
where does myelin come from?
Myelin: Schwann cells (PNS) and oligodendrocytes (CNS)
182
Where are schwann cells present and how do they myelinate an axon?
Peripheral nervous system
Schwann cells myelinate individual axons
– Surround all axons but may not myelinate
Schwann cells myelinate individual axons – can surround an axon with no myelination – ie not all Schwann cells produce myelin.
Schwann cells has large areas that are flattened
Schwann = it wraps to give the multi-layered appearance
183
Why does myelin look like it does?
• Protein – lipid – protein repeats
• Linked external proteins = intraperiod line (faint)
• Linked internal proteins = major period (dense) line
• Periodicity
– PNS = 11.9 nm
– CNS = 10.7 nm
184
What is myelin made of?
• Water = ~40%, dry lipid = 70-85%, protein = 15-30%
185
What are Cerebrosides and whats the importance of them?
any of a group of complex lipids present in the sheaths of nerve fibres
In KO mice myelin forms but develops vacuoles. Paralysis seen in aged animals
Compaction- tightens up to get irregular ‘swiss role’ appearance
If you mess up cerebroside- compaction doesn’t happen, myelin cannot compact and becomes loose
186
Name difference between CNS and PNS
```
• PNS has less:
– cerebroside
– sulfatide
• CNS has more:
– sphingomyelin
```
187
What are the proteins of CNS myelin
• Two major proteins
– Myelin basic protein (MBP)
– Proteolipid protein (PLP)
188
Describe what happens if theres a mutation in Proteolipid protein
```
• Natural mutation
– Jimpy mouse
– Very little myelin
– Die early
– Severe loss of oligos
– PLP produced (little) is toxic
– KO mice or rumpshaker = milder phenotype as don’t have toxic effect
```
189
Describe what happens if there's a mutation in Proteolipid protein
```
• Natural mutation
– Jimpy mouse
– Very little myelin
– Die early
– Severe loss of oligos
– PLP produced (little) is toxic
– KO mice or rumpshaker = milder phenotype as don’t have toxic effect
```
Lost the oligodendrocytes- reduced capacity to myelinate the axons needed
190
What happens if there's a mutation in Myelin basic protein?
• Induces experimental allergic encephalomyelitis (EAE)
– Model for multiple sclerosis
– Shiverer mice
– Die early
191
Name other CNS myelin proteins
```
• Enzymes
– Cyclic nucleotide phosphodiesterase
– Proteases
– Lipid metabolism
– Carbonic anhydrase
```
• Ig – like molecules
– MOG and MAG
– oligo-axon communication
192
Name PNS myelin proteins
```
• P0 50+% of PNS myelin protein
– Some Charcot-Marie-Tooth syndrome (CMT 1b)
– KO mice - profound myelin defects
– Adhesion molecule - compaction
• MBP
– less important here
– doesn’t cause many diseases
• PMP-22
– CMT 1a
– Can get embryonic lethal
– Heterozygous survive but there is a disruption
```
193
Describe Multiple sclerosis
```
• Onset 20’s – 40’s
• Variable severity
• Relapsing / remitting MS
• May be progressive
• MRI - plaques
• Periventricular white matter vulnerable
• Primary demyelination
– i.e. axon - sparing
```
194
multiple sclerosis- genetics vs environment
* Caucasians (f:m = 1.5:1)
* Monozygotic twins ~ 30% concordance- evidence not strong with genetics
* Linkage studies - immunological factors
* Clusters/migration/geographic distribution suggest environment. Vitamin D! (low levels)
* Virally-induction e.g. herpes.
195
Autoimmunity and multiple sclerosis
* Generally accepted
* Clear inflammatory response
* No clear evidence for any particular autoantigen
* Macrophage and protease activity degrades myelin
196
What therapy is there for multiple sclerosis?
```
• Steroids
• Interferons
– Interfere with immune response
• Other immune suppressants e.g. cyclophosphamide, antibodies e.g. alemtuzumab
• Haemopoietic stem cells
• Dietary e.g. vitamin D
```
Non-antibody-based therapies
Monoclonal antibodies which have been modified in certain ways
- Target lymphocytes
197
Guillan-barre syndrome
• Post viral/bacterial infection
– e.g. Campylobacter jejuni, Zika virus?
• Acute inflammatory response
• Primary demyelination
• Molecular mimicry?
– e.g. between LPS of bacterial coat and myelin lipids/proteins
– something about original immune response, antigen targeted mimics something in myelin so when body makes antibodies against this antigen it may recognize the myelin as foreign also
– antibody cannot tell difference between myelin and antigen
198
What does the nervous system do?
```
• System of communication that allows an organism to react rapidly and modifiable to changes in its environment
• Neurones must:
– Collect
– Integrate
– Output
```
199
How does the nervous system do its function?
* Electrical activity provides a rapid, reliable, and (flexible) means for neurones to receive, integrate and transmit signals.
* Chemical messengers (and receptors) between and within cells provide much more flexibility e.g. for inhibition.
Neurotransmitters: glutamate (most abundant), gabba (inhibitory)
200
Give Electrical properties of neurons
– Electrical signals may be divided into
• Action potentials: fixed size, all-or-nothing signals that travel along (propagate) the axon
• Graded potentials: variable size, local signals not propagated over long distances
• Action potentials can pass either way along an axon, but tend to go one way (with important exceptions)
• Graded potentials pass both ways along the neuronal membrane
– Information coding
• APs are coded by frequency as they are of a unit size
• Graded potentials are coded by size and vary according to the strength of the stimulus
201
why do neurons have a resting potential?
– Inevitable consequence of:
• Selectively permeable membrane for particular ions
• Unequal distribution of charged molecules / ions sodium/potassium
• Physical forces
202
Why is the selectively permeable membrane selective and unequal?
- Channels confer selectivity
| - Pumps assist unequal charge distribution
203
Two forces control movement of ions in aqueous solutions
Diffusion
| Electrical field
204
Describe diffusion and how lipid bilayer provides a barrier and what this leads to
Ions in solution are in constant motion and tend to distribute themselves evenly, so that there is net movement of ions from regions of ‘high’ concentration to regions of ‘low’ concentration.
The lipid bilayer provides a barrier to diffusion, so that we can end up with different concentrations of ions on either side of the membrane….ie. We have a ‘CONCENTRATION GRADIENT’
205
What do electric field cause ions to do? and what does this mean?
Electric fields also cause ions to move- opposite charges attract and like charges repel.
Because Ions are Charged- movement of ions gives rise to an electric current (represented by symbol I and measured in Amperes)
206
How much current will flow is dependent upon
Electrical potential
Electrical conductance
Ohms law- describes the relationship between potential, conductance and the amount of current that will flow, I=gV….so no current flows if g or v=0!
207
What does movement of any ion through its channel depend on?
the concentration gradient and the difference in electrical potential across the membrane
208
Whats the Ionic basis of the resting membrane potential?
- Negative Vm is an ABSOLUTE requirement for a functioning nervous system
209
Describe Ion pumps
- Ion pumps in the membrane set up the ionic concentration gradients found in neurones
- Important ion pumps:
• Na+ / K= ATPase
• Ca2+ pumps (not just in the plasma membrane)
- Without ion pumps, the resting membrane potential would not exist, and the brain would not function
- But the effects of pump inhibitors takes some time to work
210
What are Equilibrium potentials (Eion)?
* Ionic gradients influence membrane potential by determining Equilibrium Potentials Eion
* Eion is the membrane potential that would be achieved in a neurone if the membrane were selectively permeable to that ion
211
The Nernst equation
- Used to calculate the equilibrium potential (Eion) for an ion
Eion = 2.303 RT/zF log [ion]o/[ion]I where R is the gas constant and F is the faraday constant, T is absolute temperature and Z is the charge on the ion….
At body temperature (37 C) we can simplify equation to
Eion= 61.54/z log [ion]o/[ion]I
212
Ionic concentrations of a typical mammalian neurone are as follows (in mM)..
```
Intracellular Extracellular Eions
K+ 100 5 -80mV
Na+ 15 150 62mV
Ca2+ 0.0002 2 123mV
Cl- 13 150 -65mV
```
* At rest the neuronal membrane is very permeable to K+. (Slightly permeable to others)
* At rest the real membrane potential is close to but not at EK
213
Importance of Potassium channels
Potassium channels on the other hand are a key determinant of the resting membrane potential and neuronal function…because membrane is highly permeable to K at rest, changes in K concentration can have big effects. Thus increasing extracellular potassium causes a shift in Ek…if increase it, Ek becomes more positive…ie it is DEPOLARIZED.
214
The Goldman Equation
• Neurons do not have resting Vm at Eion for K+
• The resting membrane is also permeable to other ions e.g. Na+
– much less
• To estimate real Vm you need the Goldman
215
What do Nernst and Goldman equation each calculate?
* Nernst Equation can be used to calculate the equilibrium potential for an ion
* Goldman Equation calculates combined potentials
216
key points about Eion
* Ionic Driving Force (ion movement rate)
| * IDF α | Vm – Eion |
217
Calculate the predicted Vm of an interneurone whose plasma membrane is 40x more permeable to K+ than Na+. Reverse the permeability, now what’s the Vm?
look up and work out
218
Calculate the predicted Vm of an interneurone at 37oC whose plasma membrane is selectively permeable to K+. What would happen to the membrane potential if only Na+ channels were open?
look up and work out
219
How is information encoded in the nervous system?
- Action potentials
| - Graded potentials
220
Characteristical features of an action potential
(1) Rising Phase-rapid depolarization of the membrane
(2) Overshoot-where membrane potential is above Zero, in this case ~+40mv
(3) Falling Phase-rapid ‘repolarization’ of the membrane, note that it goes more –ve than the starting resting membrane potenial…
(4) Undershoot or ‘after hyperpolarization’…gradually ‘declines’ so that membrane potential comes back to ‘resting’ levels.
221
Properties of the action potential
• Transient, rapid and reversible change in membrane potential from –ve to +ve
• Different types of excitable cell may have different types of action potential
• Neuron AP often triggered by Na+ permeability increase
• AP’s or ‘spikes’ generated by a cell
– all of the same size and duration
– do not decrease as conducted down the axon
222
How are action potentials generated?
occurs when the membrane potential of a specific axon location rapidly rises and falls, this depolarisation then causes adjacent locations to similarly depolarise
223
changes in membrane permeability that underlie an action potential
- a neurone is depolarized when the permeability to Na is increased, Ena +62mV therefore if cell at rest is at Ek (-80 mV) net driving force on Na will be (Vm – Ena) = -80 -62 = -142 mV
- this is a large potential difference, so there is a very strong pull on the ions, and a big concentration gradient, so opening of Na channels leads to a rapid and large influx of Na…ie.
- Have ‘inward Na current’ .hence rapid depolarization, but after ~1 ms, the Na channels automatically snap shut , and permeability to K once again dominates
- so now have strong driving force for K and get an ‘Outward Potassium current’
224
Voltage-gated Na+ channels open in response to what? and what affects the voltage sensors?
depolarization
| Concentration of charge near plasma membrane (5nm) affects voltage sensors
225
Na+ channels inactive in a time- and voltage- dependant manner
- channel inactivation occurs quickly – 1ms (Step 3)
| - channel de-inactivation (Step 4) must occur before channels can be activated again
226
Name useful poisons of the membrane
* Tetraethylammonium, TEA. K+ channels
* Lidocaine Na+ channels
* Tetrodotoxin, TTX. Puffer fish (sp.) (fugu). Na+ channels
* Saxitoxins, STX. Dinoflagellates (sp). Na+
227
what happens once action potential is initiated in a neurone?
Needs to travel down the axon to carry the message. This occurs by spread of charged particles (the Na+ ions) although they spread in both directions, Na channels behind inactivated, so only Na channels ahead available to open…hence why action potential travels in one direction from point of initiation.
Important property of axons is that can generate action potentials (ie. Have the necessary channels!!!) along their entire length, so that action potential is propagated in a non-decremental manner.
Conduction velocity can be as fast as 10 m / sec.
228
Name and explain Factors influencing Cv
• Why diameter?
– resistance to current flow is inversely proportional to cross-sectional area of the axon
• Why myelination?
– it prevents current loss along the axon by Rm and increases the Space Constant
– Space Constant is distance from site of depolarization where it has fallen to 37%
– Ions diffuse less if myelin present
– Increases membranes resistance
– Space constant high, decays more slowly
• Why so many unmyelinated small axons?
– because the space constant Rm / Ri so the benefit of a high membrane resistance is reduced by the high internal resistance
– metabolic and volume costs of myelination
– Space constraint- only have a certain amount of space in the brain
– Only when we need to transmit a signal a long distance
– If local transmission, no myelination needed
– Need lots of energy to myelinate- not cost efficient
229
give examples of conduction velocity in myelinated and unmyelinated axons
* Smallest unmyelinated axons around 0.2 – 1.5m = 0.5 – 2 m/s
* Most axons > 1.0 m are myelinated, 1 - 20 m = 5 – 120 m/s
* Squid giant axon 1000 m = 25 m/s
230
Ion channels have restricted distributions- Saltatory conduction
Focal accumulations of Na+ channels
Myelin increases speed and distance that action potentials travel
No generation of action potential, if continuous myelin sheath
Therefore, there are node of Ranvier containing many sodium ion channels
Enough for depolarising membrane
231
Describe Dendrites
- Dendrites have voltage-sensitive channels but don’t usually produce AP’s
- Dendrites mostly encode information with graded potentials
Dendrites generates graded potentials, have voltage-sensitive channels but don’t have the properties to create an action potential
232
Coding by action potentials
Continuous stimulation of a neuron produces a ‘train’ of action potentials
The FREQUENCY of the action potentials is dependent on the size of the depolarizing stimulus…the stronger the stimulus (ie. The more positive) … the higher the frequency
…this provides a way to encode stimulation intensity in the nervous system.
…there is however a limit to the frequencies that can be achieved:
233
What's the absolute refractory period?
~1 ms no matter what you do, the neuron is incapable of generating another action potential…this is often followed by
234
What's the relative refractory period?
a few more ms) during which you can fire another action potential, but you would require a stronger stimulus because the ‘threshold’ is raised.
235
Stimulus intensity is encoded by what?
action potential frequency in the nervous system
Different levels = different spiking rates
Higher the depolarisation the higher the frequency of actionpotentials
236
What are graded potentials?
are changes in membrane potential that vary in size, as opposed to being all-or-none. They arise from the summation of the individual actions of ligand-gated ion channel proteins, and decrease over time and space
237
Two types of graded potentials
- Excitatory post synaptic potentials (depolarises membrane- increase)
- Inhibitory post synaptic potential (hyperpolarises membrane- decrease)
238
What can Graded potentials do?
can summate -Act to integrate information from multiple neuronal imputs
239
What's temporal summation?
Temporal summation occurs when a high frequency of action potentials in the presynaptic neuron elicits postsynaptic potentials that summate with each other. The duration of a postsynaptic potential is longer than the interval between action potentials.
240
What's spatial summation?
Spatial summation. Spatial summation is a mechanism of eliciting an action potential in a neuron with input from multiple presynaptic cells. It is the algebraic summing of potentials from different areas of input, usually on the dendrites.
241
what can be ‘shunted’ by inhibitory inputs
An excitatory postsynaptic potential
242
What is an excitatory postsynaptic potential?
An excitatory postsynaptic potential (EPSP) is the change in membrane voltage of a postsynaptic cell following the influx of positively charged ions into a cell (typically Na+) as a result of the activation of ligand-sensitive channels.
243
Electrical synapses are important for what cells?
* Retinal neuronal
* Few other adult CNS neurons, (glial junctions)
* Cardiac muscle
* Smooth muscle
