Neuroscience and Mental Health Flashcards
The nervous system is divided (2)
Central Nervous System
Peripheral Nervous System
CNS includes
Brain
Spinal Cord
PNS includes
Nerves
Ganglia (clusters of neuronal cell bodies)
PNS functionally divided into (2)
Somatic (motor and sensory divisions)
Autonomic (motor and sensory divisions)
What is the Somatic PNS?
Controls motor and sensory function for the body wall e.g. skin (sensory neurone) and skeletal muscles (motor neurone)
What is the Autonomic NS?
Visceral PNS, vegetative NS, involuntary NS
Regulates function of the viscera (internal organs, smooth involuntary muscle, pupils, sweating, blood vessels, bladder, intestine, glands etc.)
Controls heart contraction rate
Has sympathetic and parasympathetic arms
The type of nerves in the sympathetic division of the ANS are…
Spinal nerves
The type of nerves in the parasympathetic division of the ANS are…
Spinal nerves
Cranial nerves
The type of nerves in Somatic NS are…
Spinal nerves
Cranial nerves
Brain is composed of (3)
Cerebral cortex (cerebrum)
Cerebellum
Brainstem
Describe the input/output to cerebral cortex
2 hemispheres
Each receives sensory info and controls movement of opposite side of the body
What is the function of the cerebellum?
Controls motor coordination (movement) and involved in learning motor skills
Describe the brainstem
Most primitive part
Densely packed fibres
Regulates vital functions (e.g. consciousness, breathing)
Damage here usually serious (can be fatal)
What are the dorsal and ventral roots of the spinal cord?
Dorsal and ventral roots that emerge from the SC
Are part of the PNS
Describe the overall process of neurotransmission (not ions just overall action of NTs)
An AP reaches a neuronal chemical synapse
NTs released by presynaptic terminal bind to post-synaptic receptors
What are the differences between the regenerative capacities of injured axons in the CNS and PNS?
CNS
Unable to regenerate over long enough distances to be useful
Inhibitory molecules
PNS
Axons in PNS can regenerate after injury
No inhibitory molecules
How is regeneration/recovery compromised in the NS?
Recovery compromised by non-specific target re-innervation and aberrant axon sprouting
Absence of guidance cues to stimulate axon growth during development
Define: Afferent axons
Axons entering CNS
Propagate APs towards brain and spinal cord from PNS
E.g. sensory neurons (somatic and ANS)
Define: Efferent axons
Axons leaving CNS
Propagate APs from brain and spinal cord to PNS
E.g. motor neurons (somatic and ANS)
Define: Interneurons
CNS neurones that synapse with other CNS neurones within brain or spinal cord
What do somatic sensory neurons convey?
Convey sensory info from body to SC and then there to sensory cortex
Stimulate reflex activity
Where is sensation perceived?
Sensory cortex
Are the sensory and motor cortex anatomically distinct?
Yes
What does white matter comprise of?
Ascending and descending axon tracts to/from the brain
What are needed for a reflex response?
Somatic sensory inputs-> (interneurons)-> motor outputs from SC
Neurones must be intact
NOT communication with sensorimotor cortex
What is required for conscious registering of a sensory stimulus?
Sensory inputs activate sensory neurones in grey matter of SC (ascending tracts-> sensory cortex of the brain)
What happens to neurones from the motor cortex?
Axons extend downward to synapse with spinal motor neurones and transmit APs (descending tracts)
Important for voluntary movement
CASE
Lost voluntary movement and sensation in L arm
Muscles show reflex activity
CAUSE?
Likely to be injury to R hemisphere Close to sensorimotor cortex Not peripheral nerve (reflex intact) Not SC (only 1 arm) Probably stroke
CASE
Lost voluntary movement and sensation in L arm
Muscles don’t show reflex activity
CAUSE?
Likely to involve periphery (lose reflex)
Not SC (only 1 arm)
Probably due to fall
CASE
Lost voluntary movement in L arm and leg
Muscles show reflex activity
CAUSE?
Likely to be in R brain sensorimotor cortex (leg and arm region)
Not peripheral (reflex intact)
Not SC (only 1 side)
Probably brain tumour? Stroke?
What is neurology?
Study of brain, SC, peripheral nerves and muscle
What components are there in a standard neurological exam?
Gait and station Cranial nerves Motor Sensation Mental state
MMSE (mini mental state exam) categories
Orientation
Registration
TRIALS
Attention and calculation
Recall
Language
MMSE: Orientation
Year, season, date, day, month
Country, city, part of city, house no., street name
MMSE: Registration
3 objects said by Dr
Repeated until patient remembers all 3
Count trials and record
MMSE: Trials- attention and calculation
Serial 7s- 1 point for each correct
Stop after 5
OR
Spell ‘world’ backwards
MMSE: Trials- Recall
Ask for 3 objects in registration phase
MMSE: Trials- Language
Name certain items, repeat certain phrases, follow 3 stage command etc.
5 stages of diagnosing neurological problems
Approach (present signs and symptoms to ID underlying anatomy-> characterise syndrome)
History (nature/onset of symptoms, family/social history, prev. medical problems)
Examination (MMSE, nerves, limbs)
Investigation (scans, lumbar puncture, EMG, EEG, pathology)
Syndromic formulation
What does an EEG do?
Electroencephalography
Measures electrical potentials at scalp generated by underlying neurones
Useful for diagnosing epilepsy and coma
What are EMG and NCS used for?
Electromyography and nerve conduction studies
Examines integrity of muscle, peripheral nerve and lower motor neurones
How are CTs used in neurological diagnosis?
Computerised tomography
Uses X-ray source, high conc. of ionising radiation
Shows hard tissues well
Relatively fast and inexpensive
How are MRIs used in neurological diagnosis?
Based on behaviour of H protons in the tissues to a strong, externally applied magnetic field
Good for differentiating soft tissues
Don’t use ionising radiation
Non invasive
What do lumbar punctures study and where can it be obtained from?
Cerebrospinal fluid
Between L3 and L4 AND L4 and L5
What can be used for neurological diagnosis?
Neurophysiology= EEG, EMG, NCS
Imaging= CT, MRI
Lumbar puncture
What causes a stroke?
80% blockage of blood vessel (infarct- which may be caused by carotid arteries in neck)
20% bleeding (haemorrhage often related to high BP)
Where can strokes affect?
Any part of the brain (including brainstem)
Tends to cause problems contralateral to brain lesion
Symptoms relate to which artery in brain is affected
What are stroke risk factors?
Smokers
Family history
Diabetes
Excess alcohol
Why can strokes cause aphasia?
Left side of brain responsible for language
Strokes here can lead to aphasia
Where do strokes most commonly affect and what symptoms does it cause?
Middle cerebral artery
Results in weakness and loss of sensation on the other side
What are the symptoms of posterior cerebral artery strokes?
Affect occipital lobe
Result in visual loss on contralateral side
What are the symptoms of anterior cerebral artery strokes?
Often cause contralateral leg weakness
What are the symptoms of strokes affecting the brainstem?
Problems with balance
Eye movements
Speech and swallowing
Breathing
Stroke treatment: Acute
Intravenous thrombolysis- dissolve clot
Intra-arterial thrombectomy- remove clot
Stroke treatment: Complications
Neurosurgery for haemorrhage or dangerously high pressure
Stroke treatment: Prevent further stroke
Thin blood with aspirin
Treat diabetes and high cholesterol
Treat dangerously narrow carotid arteries
What neurotransmitter is associated with Parkinson’s disease?
Dopamine
What are PD patients treated with? And why not Dopamine?
Levodopa
Dopamine doesn’t cross BBB but levodopa crosses BBB and then converted into dopamine
Also treated with deep brain stimulation (DBS)
What are the causes of Spastic Parapesis?
Trauma
Inflam/autoimmune (e.g. MS)
Neoplastic (e.g. SC tumour)
Degenerative (e.g. motor neurone disease)
Vitamin deficiency (b12)
Infection (e.g. syphilis)
Vascular (anterior spinal artery thrombosis)
—> sensory level
What is Multiple Myeloma?
Tumour of plasma cells
Treated with radiotherapy and chemotherapy
What causes Acute Polyneuropathy?
Infections e.g. Diptheria
Autoimmune e.g. Guillain Barre
Drugs e.g. chemo
Exposure to toxins e.g. organophosphate insecticides
What is GBS/AIDP?
Common cause of acute neuromuscular weakness
Clinical diagnosis
Progressive ascending sensorimotor paralysis with areflexia, affecting 1 or more limbs and reaching nadir within 4 weeks
Patients may progress to almost complete paralysis and require ventilation
What is the treatment for GBS/AIDP?
Immunotherapy= plasma exchange or IV immunoglobulin
Supportive e.g. ventilation
Cardiac monitoring
Anticoagulation to prevent leg clots (and subsequent pulmonary emboli)
What are the symptoms of Parkinsonism?
Impassive faces Soft, monotonous speech Slow shuffling gait Stooped Loss of arm swing Pill-rolling tremor Increased tone and cogwheeling Bradykinesia Micrographia (small handwriting)
What is a neurone?
Basic structural and functional unit of the NS
Info processing
Responsible for generating/conducting electrical signals
Supported by neuroglia
Highly organise metabolically active secretory cell
What is the ratio neuroglia:neurones
9:1
Describe neuronal structure
Cellular structure of all neurones is similar (diversity achieved by differences in number and shape of their processes)
Large nucleus Prominent nucleolus Abundant RER Well developed Golgi Abundant mitochondria Highly organised cytoskeleton
What is a dendrite (input)?
Dendritic spines receive majority of synapses/info
Spread from cell body
Increase s.a. of neurone
Often covered in spines (protrusions)
NB. Large pyramidal neurones may have 30,000-40,000 spines (pyramidal cell body in pyramidal cells)
What is an axon (output)?
Conduct impulses away from cell body Emerge at axon hillock Usually 1 per cell (may branch) Contain abundant intermediate filaments and microtubules Can be myelinated or unmyelinated Cable properties Organised into (molecular) domains
What are the domains in an axon?
Paranode
Node
Juxta-paranode
What is an axon terminal?
Axons often branch extensively close to target (terminal arbor)
From synaptic terminals with target
Either bouton (synapse) or varicosities (in smooth muscle cells)
What are synapses?
Between cells
Contain synaptic vesicles containing neurotransmitters
Vesicles fuse with axon membrane and release NT which reacts with synaptic vesicles
Specialised mechanisms for association of synaptic vesicles with the plasma membrane
Abundant mitochondria needed for ion pumping and synaptic transmission
Neurones can be excitatory, inhibitory or modulatory. Which types are which?
Axo-dendritic= often excitatory Axo-somatic= often inhibitory Axo-axonic= often modulatory
Neurofilaments play a critical role in what (to do with neuronal cytoskeleton)?
Axon caliber
Name the main intracellular transport types (functional polarization)?
Fast axonal transport
Anterograde transport
Retrograde transport
What is fast axonal transport?
Transport of membrane associated materials
Vesicles with associated molecular motors (moved down axon at 100-400mm per day)
Different membrane structures targeted to different compartments
What is anterograde transport?
Transport of materials needed for neurotransmission and survival away from cell body
Fast or slow
Fast= synaptic vesicles, transmitters, mitochondria
Uses microtubular network and requires oxidative metabolism
Slow= bulk of cytoplasmic flow of soluble constituents
What is retrograde transport?
Fast= return of organelles
Transport of substances from EC space
Uses different molecular motors
E.g. Trophic growth factors, neurotrophic viruses
What is the size range of cell bodies?
5 micrometers to 135 micrometers
Describe DRG sensory neurones
Pseudounipolar
2 fused axonal processes
No dendrites (receive no synapses)
Have a soma
Describe bipolar neurones?
Two axonal processes with central soma
E.g. in cerebral cortex, retina
Describe Golgi Type I Multipolar cells
Highly branched dendritic trees
Axons extend long distances
E.g. pyramidal cells of cerebral cortex, purkinje cells of cerebellum, anterior horn cells of spinal cord, retinal ganglion cells
Describe Golgi Type II Multipolar cells
Highly branched dendritic trees
Short axons terminating quite close to the cell body of origin
E.g. stellate cells of cerebral cortex and cerebellum
Describe pyramidal cells of the cerebral cortex
Golgi Type I multipolar
Major excitatory neurones
Single axon with triangular shaped soma
Large apical dendrite which arises from apex of principle cell’s soma
Basal dendritic tree consists of 3-5 primary dendrites (profuse branching)
Describe stellate cells of the cerebral cortex and cerebellum
Golgi Type II multipolar
Major excitatory input to cortical pyramidal cells
Small multipolar cells with local dendritic and axonal arborizations
Use glutamate or aspartate as a NT
What are the functional subtypes of neurones?
Sensory (generally pseudounipolar-> 1 to CNS, 1 to sensory receptor)
E.g. DRG neurones
Motor (generally multipolar with large soma)
E.g. spinal motor neurones
Interneurons (can be multipolar or small bipolar local circuit neurons)
What are the functional organisational groups of neurones?
Nucleus Laminae Ganglion Fibre tracts Nerves
Functional organisation: describe nucleus
Group of unencapsulated neuronal cell bodies within the CNS
Usually consist of functionally similar cells
E.g. Raphe nuclei
Functional organisation: describe laminae
Layers of neurones of similar type and function
E.g. cerebral cortex grey matter
Functional organisation: describe ganglion
Group of encapsulated neuronal cell bodies within the PNS
Functional organisation: describe fibre tracts
Groups or bundles of axons in the CNS
Mixture of myelinated and unmyelinated
E.g. corpus callosum, internal capsule
Functional organisation: describe nerves
Discrete bundles of axons
Bring info to CNS and to effector organs
Often mixed sensory and motor neurones
Usually part of PNS
Describe the role of neuroglia
Support cells of the nervous system
Astroglia, oligodendroglia, microglia, immature progenitors, ependymal cells, Schwann cells, satellite glia
Many and varied functions
Essential for the correct functioning of neurones
Describe astroglia
Multi-processed star-like shape
Most numerous cell type
Numerous intermediate filament bundles in cytoplasm of fibrous astroglia
Gap junctions suggest astroglia-astroglia signalling
Describe the functions of astroglia
Scaffold for neuronal migration and axon growth
Development
Formation of BBB
Transport of substances from blood to neurones
Segregation of neuronal processes
Removal of neurotransmitters
Synthesis of neurotrophic factors
Neuronal-glia and glial neuronal signalling
Potassium ion buffering
Glial scar formation
Barrier functions
What are oligodendroglia?
Myelin forming cells of the CNS (Interfasicular oligodendroglia and perineuronal oligodendroglia) Small spherical nuclei Few thin processes Prominent ER and Golgi Metabolically highly active
What are the functions of oligodendroglia?
Produce/maintain myelin sheath
Each cell produces multiple sheaths (1-40)
What is myelin?
Lipid rich insulating membrane up to 50 lamellae
Dark and light bands at EM level
Loss of oligodendroglia and myelin has disastrous consequences
What diseases are caused by faulty myelin?
Multiple sclerosis
Adrneoleucodystrophy
What are microglia?
Derived from bone marrow during early development
Resident macrophage population of the CNS
Involved in immune surveillance
Present antigens to invading immune cells
First cells to react to infection or damage
Role in tissue remodelling
Synaptic stripping
Phagocytic when diseased (in inflammation)
What are peripheral glia?
Schwann cells Myelin producing cells of the PNS Each Schwann cell produces only 1 myelin sheath Surround unmyelinated axons Promote axon regeneration
Define Multiple Sclerosis
A chronic inflammatory multifocal demyelinating disease of CNS of unknown cause
-> Loss of myelin and oligodendroglial and axonal pathology
Typically affects young adults
Exacerbating-remitting pattern or chronic progessive evolution
Need 2 or more clinical attacks= dissemination in time and space
Symptoms of MS
Visual e.g. double vision Motor (evenutal paralysiss) Sensory Cognitive and psychiatric Bowel, bladder Sexual Speech issues Vomiting Off-balance= dizzy
Onset= hours to days Recovery= days to months
How do you diagnose MS?
Clinical history
MRI (hyperintense white spot signals)
CSF analysis (increased immunoglobulin production)
-> Oligoclonal bands by electrophoresis (has to be matched with blood)
What are the clinical subtypes of MS?
Relapsing-remitting (complete or incomplete recovery relapses) Secondary progressive (relapses with increased worsening of disability and recovery) Primary progressive (increased disability with no recovery)
Epidemiology of MS
20-40 years old
More frequently in females
What therapy is used for MS?
Immuno-modulatory and immuno-suppressive treatments are aimed at reducing relapses
Steroids given to patient for his attacks
Treatments to attenuate symptoms (pain, spasticity, bladder dysfunction)
Define: flux (relevant to diffusion)
Rate of transfer of molecules
E.g. no. of molecules that cross a unit area per unit of time (m2/s)
No net flux at dynamic equilibrium
What are the properties of ions?
Charged molecules
Opposite charges attract
Like charges repel
Units of electrical properties
Voltage (pd)= volts (ions produce a charge gdt)
Current= amps (movement of ions due to pd)
Resistance= ohms (barrier that prevents movement of ions)
How do you measure membrane potential?
Reference electrode placed outside cell (0V level)
Another electrode inside cell
Measures voltage difference (-ve compared with outside)
All cells have a membrane potential
Describe ion channels
Permeable pores in membrane that open and close depending on trans-membrane V, ligands or mechanical forces
Can be selective for different types of ion
Allows membrane to selectively allow ions to cross
Define electrochemical equilibrium
For an ion reached when its concentration gradient is balanced by the electrical gradient across the membrane
What is the Nernst equation and what does it show?
Equilibrium potential of X ion (mV)
SEE FORMULA
R= gas constant T= temp (Kelvin) Z= valency F= Faraday's number (coulombs of charge per mol of ion) Ln= natural log
Recall typical concentrations for ions (IC and EC)
.....ION..... EC..... IC..... Na 150mM 10mM K 5mM 150mM Ca 2mM 0.0001mM Cl 110mM 5mM Organic phosphates 3mM 130mM pH 7.4mM 7.1mM Osmolarity 285mosmol/l (EC+IC)
What is the equilibrium potential for K+?
-90mV
What is the equilibrium potential for Na+?
+72mV
What is the typical Em?
-70mV
Membrane more permeable to K
Why is the membrane closer to K+ equilibrium potential?
K diffuses out of cell (through permanently open channels)
Inside of cell becomes negative
Membrane slightly permeable to Na which cancels out equivalent number of K ions
This means real membrane potential more +ve than K equilibrium potential
K leaky channels
What is the Goldman Hodgkin Katz equation?
Describes the real resting membrane potential
Influenced by Na, K and Cl
Size of each ions’ conc is proportional to how permeable the membrane is to the ion
What do different values for P (permeability/channel open probability) mean?
0= 100% closed 1= 100% open 0.5= open 50% of time
Work out mV for….
All channels open all the time
Only K channels open (Cl and Na closed)
K channels open, Na permeability 5% and Cl closed
- 14mV
- 90mV
- 66mV
Which membrane potential tends towards 0 (away from RMP)?
Depolarising
Which membrane potential tends above zero towards Na equilibrium potential?
Overshoot
Which membrane potential tends away from RMP but in same direction as repolarisation (leads to membrane potential closer to K equilibrium potential)?
Hyperpolarising
Which membrane potential tends towards the RMP?
Repolarising
What are graded potentials?
Change in membrane potential in response to stimulation and occur at synapses and sensory receptors
Contribute/initiate/prevent APs
Defining characteristics of graded potentials?
May be depolarising or hyperpolarising depending on stimulus
Magnitude of membrane potential dependent on strength of stimulus and decreases over time/distance from stimulus site
What is decremental spread? (Regarding graded potentials)
Magnitude of membrane potential change decreases with time and with distance from stimulus site
What effect does temperature change have of equilibrium potential of an ion?
Increased temp-> increased permeability-> membrane leaky
What are regenerative capacities?
CNS axons don’t spontaneously regenerate after injury in adult mammals
PNS axons readily regenerate, allowing recovery of function after peripheral nerve damage
What are action potentials?
Occur in excitable cells
Nerve impulses that allow transmission of info reliably and quickly over long distances
Important in cell-to-cell communication and can be used to activate IC processes
What cells are electrically excitable?
Muscle fibres
Neurones
Define: Threshold
Critical level to which a membrane potential must be depolarized to initiate an AP
Necessary to regulate and propagate signalling in both CNS and PNS
Define: Refractory state
Period immediately following stimulation during which a nerve or muscle is unresponsive to further stimulation
Define: All or nothing
Once triggered, a full sized AP occurs
Define: Saltatory conduction
Propagation of APs along myelinated axons from one node of Ranvier to next node, increasing conduction velocity of APs
Define: Voltage-gated ion channels
Transmembrane ion channels activated by changes in electrical membrane potential near the channel e.g. for Na and K
Define: Channel inactivation
Conformational change of a channel protein by which the channel goes from the open
State to permeate the channel pore
Occurs in sodium channels in APs
Define: Positive feedback
Enhancing or amplification of an effect by its own influence on the process which gives rise to it
Occurs in Na channels in AP
Sequence of events in typical AP
RMP Depolarizing stimulus Upstroke Repolarisation Hyperpolarisation RMP
What causes the upstroke in an AP?
VGSCs open quickly
Increased permeability to Na
Na enter cell down electrochemical gradient
VGPCs open slowly
Slightly increased permeability to K
K leave cell down electrochemical gradient
Less than Na entering
Membrane potential moves toward Na equilibrium potential
What causes repolarization in an AP?
VGSCs inactivated
Decreased permeability to Na
Na entry stops
More VGPCs open and remain open Increased permeability to K
K leaves cell down the electrochemical gradient
Membrane potential moves toward K equilibrium
What is the absolute refractory period?
Inactivation gate is closed
New AP can’t be triggered even with very strong stimulus
What causes hyperpolarization in an AP?
At rest, VGPCs are still open
K continues to leave cell down electrochemical gradient
Membrane potential moves closer to the K equilibrium
Some VGPCs then close
Membrane potential returns to the resting potential