Neuro Flashcards
What are proprioceptors?
the type of sensor receptors that monitor the movements of our own bodies. They allow you to know where your body is and provide vital feedback information for the control of motor systems.
What do muscle spindles detect?
the stretch of muscle
What is the very basis of neurones and muscle fibres in motor control?
there is a single synapse to each of the muscle fibres. Each action potential in the motor neurone will produce one in each of the four muscle fibres, and they will then twitch.
Twitches are all or nothing events - how can the force of contraction be modified?
- change the frequency of action potential firing in the active motor units
- change the number of active motor units
- change the type of active motor units
This is how movements are ‘graded’.
What aspects may affect how much excitatory input needs to go to a cell to reach its action potential?
- bigger cell body = bigger input
- small ‘red’ motor units are more easily excited, so they are recruited first
How do muscle spindles control posture?
- muscle contracting too little to overcome gravity
- spindle stretched, increasing afferent activity
- increased excitation of the motor neurone pool
- increased force of contraction
What is the structure surrounding gamma motor control?
- fusiform capsule
- intrafusal fibres inside the capsule
- only have actin myosin contractile machinery at the ends
- the afferents associated with the muscle spindle are associated with the stretchy middle bit and are only affected when it stretches
What happens in gamma motor control?
- muscle stretches as part of a voluntary movement
- intrafusal centres do not stretch, so afferent activity unchanged
- no excitation of motor neurone pool
- muscle doesn’t resist stretching
Muscle spindles also ensure accuracy of movement.
What happens in gamma motor control when you pick up something which is heavier than you expected?
- muscle shortens too slowly, but intrafusal ‘poles’ are not loaded so they shorten as intended
- intrafusal centres stretch, increasing afferent activity
- increased excitation of the motor neurone pool
- increased force of contraction ‘corrects’ the movement
Contraction can also be influenced by inhibition
What happens in inhibition of gamma motor control?
- muscle stretches as part of a voluntary movement
- descending control systems activate inhibitory interneurones
- reduced activity in the motor neurone pool
- muscle doesn’t resist stretching
What is reciprocal inhibition?
- Ia afferents excite interneurons that directly inhibit antagonist motor neurones
- these interneurones are glycinergic
- they act through ligand-gated receptors on the motor neurone itself
What is presynaptic inhibition?
- Ia afferents excite interneurones that inhibit release of neurotransmitter from antagonist Ia afferents
- these interneurones are GABAergic
- they act through metabotropic receptors (GABAb) on the axon terminals
What are lower motor neurone lesions?
In skeletal muscle, ‘lower motor neurone’ = alpha motor neurone
Lower motor neurone lesions denervate the muscle, causing FLACCID WEAKNESS
- weakness
- wasting
- loss of reflexes
- fasciculations and fibrillations
What are upper motor neurones?
An upper motor neurone carries signals from the brain to the spinal motor circuits.
How do upper motor neurones initiate and control movement?
- controlling alpha motor neurones
- controlling gamma motor neurones
- controlling inhibitory interneurones
Motor neurones in the brain have axons which descend through the spinal cord which terminate where they can activate the inhibitory control.
What does loss of upper motor neurones result in?
- weakness (brain can’t tell muscles to contracT)
- increased muscle tone and reflects (brain can’t control reflex arcs)
- no wasting (muscles remain active due to reflex input)
Where is an upper motor neurone lesion?
Upper motor neurones are in the brain, but an upper motor neurone LESION can be anywhere between the cell body and the LMN.
What two classes can the intrafusal muscle fibres be divided into?
- ‘nuclear bag’ fibres are associated with ‘type Ia afferents’
- ‘nuclear chain’ fibres are associated with ‘type II’ afferents (and type Ia to some extent)
- group II afferents encode length of muscle
About group II afferents…
- thinner, slower axons
- mainly indirect connection to alpha motor neurones
- response in proportion to length of muscle
- important for maintaining limb position and posture, and for resting muscle tone
Loss of upper motor neurone input to group II reflexes causes hypertonia
How can hypertonia (from UMN lesions) be treated?
- by suppressing the group II reflex
- boosting noradrenergic transmission helps (mechanisms uncertain): alpha 2 agonists (e.g. tizanidine) and L-DOPA
About group Ia afferents…
- thicker, faster axons
- monosynaptic connection to alpha motor neurones
- responds to the rate of change in length (e.g. velocity of movement)
- important for correcting rapid unintended movements e.g. perturbations of gait
loss of upper motor neurone input to group Ia reflexes causes a velocity-dependent increase in tone (spasticity)
How can spasticity (from UMN lesions) be treated?
- need to damp down the group Ia reflex
- this can be done by a non-specific increase in spinal inhibition: boost the effectiveness of GABAa receptors - benzodiazepines
- or more specifically by mimicking the effect of presynaptic inhibition: activate GABAb receptors (baclofen)
In what circumstances are stretch receptors not always suppressed during voluntary movements?
- they are ‘switched on’ at key moments during some stereotyped movements…
- including a burst of activity in the afferents
- which boosts muscle excitation when needed
e.g. adds force to the contraction of the flexor muscles as they life the foot off he ground during walking
What do golgi tendon organs do?
measure tension generated by active muscle contraction
How do golgi tendon organ (GTO) afferents control the strength of muscle contraction?
GTO afferents activate two pathways that control the strength of muscle contraction. Upper motor neurones control which is active at any moment.
The two pathways are GTO driven INHIBITION and EXCITATION
How is the boosting of excitation done in relation to GTO?
in dynamic situations (e.g. walking) a pathway via an excitatory interneurone is enabled. This is used to boost muscle contraction at key points in the gait cycle.
What are the two ways that the gold tendon organ can work?
- loss of GTO driven inhibition will cause hypertonia in static situations (e.g. standing)
- loss of GTO driven excitation will cause weakness in dynamic situations (e.g. gait)
What is the very basics of local anaesthetics?
- act locally, as they are applied to discrete areas of the body
- prevent perception of pain by CNS - block generation/conduction of action potentials (APs) by inhibiting voltage-gating Na+ channels
What is the importance of the pH of local anaesthetics?
local anaesthetics are weak bases (pKa of 7-9)
- they act as proton acceptors at physiological pH (7.2) - more LA is in ionised/membrane impermeable form
- act as proton donors in alkaline conditions (pH>7-9) - more in in non-ionised/membrane permeable form
Why does LA procaine have a shorter half life than than LA lignocaine?
Because ester bones are susceptible to hydrolysis, and procaine has an ester bond where lignocaine has an amide bond
How does the generation and conduction of action potentials occur?
- Resting membrane potential is ~ -75mV
- high K+ inside cell ~140mM/low K+ outside cell ~6mM - due to Na+/K+ ATPase
- membrane selectively permeable to K+ ions (so negative inside cell) - during stimulation membrane depolarises to ~ -50mV
- membrane depolarisation
- reaches threshold of Na+ channels
- opens channels and depolarisation (downstroke of APs)
What is the mechanism of action of local anaesthetics?
LAs block Na+ channels:
- block generation and conduction of APs
- no APs, no information sent to CNS, no perception of pain
- local anaesthetics will block any voltage-dependent Na+ channel irrespective of the tissue
- hence these drugs are given locally to reduce systemic effects
What is the effect of pH on local anaesthetics?
There is an interesting point with local anaesthetics:
- action of LAs are increased in alkaline pH
- but ionised LAs more effective at blocking Na+ channels
Why does pH have an effect on local anaesthetics?
- LAs act on the part of the Na+ channel structure that is accessed from the inside of the cell
- alkaline pH makes more drug into non-ionised form (LA), which can cross the ‘fatty’ myelin sheath and axonal membrane
- inside the cell (pH 7.2), more drug becomes ionised into the LAH+ form, which blocks the Na+ channel - remember ‘ion trapping’
How do LAs block Na+ channels?
Mechanisms of blocking Na+ channels by LAs:
- some block of closed state: unionised state
- some block of open state: ionised state
- substantial block of channels in inactivated state - ionised state
What are ‘use-dependent’ drugs?
- LAs that only block Na+ channels in the inactivated state
- only work when there is high activity
- less side effects, low activity neurones not affected
- principle of other drugs; anti-epileptic, class I cardiac anti-arrhythmic
Why are pain fibres blocked before other sensory or motor neurones, when all fibres use Na+ channels to generate and conduct APs?
- LAs block small diameter axons before large ones
- LAs usually block unmyelinated before myelinated fibres
- nociceptive impulses are conducted in Adelta fibres (small diameter myelinated axons) and C fibres (unmyelinated axons)
- pain sensation is lost first - increasing concentration/time LAs block all axonal conduction causing local paralysis (remember loss of movement after injection of LA at dentist)
What are some unwanted effects of LAs on the CNS?
- if LAs enter the brain, this leads initially to stimulations (tremor, agitation and may produce convulsions)
- subsequent CNS depression, respiratory problems
What are some unwanted effects of LAs on the CVS?
- decreased cardiac output due to LAs blocking cardiac Na+ channels which leads to decreased Ca2+ influx and decreased force of contraction
- increased vasodilation, due to inhibition of sympathetic nerve activity innervating blood vessels - decreases vascular tone
- both these actions will cause a decrease in blood pressure –> potentially effect blood flow to vital organs
What are possible bought of administration of LAs?
- SURFACE ANAESTHESIA: applied to mucosal surface e.g. bronchial (bronchoscopy), nose, cornea - LAs do not cross skin very well
- NERVE BLOCK: LA injected close to sensory nerve e.g. dentistry
- SPINAL ANAESTHESIA: LA injected into subarachnoid space between second and fifth lumbar vertebrae enters straight into CSF, e.g. surgery when inappropriate to use general anaesthetic, hip replacement in elderly
- EPIDURAL: LA injected into epidural space, outside meninges, where it diffuses to and blocks nerve roots e.g. childbirth
What happens when LAs are administered with adrenaline?
LAs can be administered with adrenaline. Adrenaline produces vasoconstriction by acting on alpha1 adrenoceptors on vascular smooth muscle cells within the walls of blood vessels.
Vasoconstriction keeps the LA localised to the area of injection. Vasoconstriction inhibits absorption of the LA from the extracellular spaces into the blood - reduces possibility of systemic toxicity.
It also prolongs the LA action.
What do you need to beware of when administering adrenaline with LAs?
- local hypoxia
- absorption of adrenaline –> arrhythmia
Where is the primary motor cortex?
The pre central gyrus of the frontal lobe, just anterior to the central sulcus.
What does the primary motor cortex control?
voluntary movement of the opposite half of the body. Also called the motor strip, or M1.
Where is the premotor cortex and what does it do?
Immediately infront of the motor strip and it is involved in movement planning and preparation.
Where is the primary somatosensory cortex?
Just behind the motor strip, in the post central gyrus of the parietal lobe.
What does the primary somatosensory cortex do?
received ascending (sensory) projections for all sensory modalities including light touch, joint position sense, pain, temperature etc.
It is also called the sensory strip, S1
What is the homunculus?
Motor cortex: size of cortical representation of each body part in proportion to precision of motor control
Sensory: amount of cortex devoted to each body part is proportional to tactile sensitivity
In both areas the hands, face and tongue have disproportionately large representations.
What parts do the upper/lower body occupy in the primary motor and sensory areas?
In primary motor and sensory areas there is an orderly point-to-point representation of the opposite half of the body.
The lower part of the body including the lower limbs occupies the medial surface of the hemisphere.
On the convexity, the upper limb and hand areas are superior and the face/tongue areas or inferior.
What are the two parts of the primary motor pathway?
- the corticospinal tract
- the corticobulbar pathway
sometimes referred to collectively as the pyramidal tract or pyramidal motor system as the corticospinal component passes through the pyramids of the medulla.
What does the corticospinal tract do?
projects from the motor and premotor areas of the frontal love to all levels of the spinal cord. It controls voluntary movements of the contralateral (opposite) limbs/trubnk and consists of approximately one million axons each side.
What does the corticobulbar pathways do?
It is the voluntary motor supply to the brain stem (the motor cranial nerve nuclei) and therefore controls movements of the jaw, face tongue, larynx and pharynx. The word ‘bulb’ is an old fashioned term for the lower brain stem.
Where do the fibres of the corticospinal tract originate?
- About 2/3 of the fibres originate from the motor and premotor areas of the frontal lobe
- axons project to anterior horn of spinal cord grey matter (influence spinal motor neurones)
- the remaining 1/3 arise from parietal lobe
- project to dorsal horn of spinal cord, helping to ‘filter out’ sensations generated by movement
What is the pathway of the fibres of the corticospinal tract?
- leave the cerebral cortex to enter subcortical white matter
- pass through corona radiate first before entering the posterior limb of the internal capsule
- internal capsule is an anatomical bottleneck so the arrangement of motor fibres is contact so even tiny amount of damage can lead to paralysis
- continues to descend through anterior part of brain stem
- pass in turn through CRUS CEREBRA, BASILAR PONS and then the PYRAMIDS OF THE MEDULLA
- crosses the midline at the lowermost border of the medulla (approx at foramen magnum)
- 90% of fibres cross posteriorly and laterally to enter lateral column of spinal cord as the lateral corticospinal tract
- remaining 10% continue in the anterior part of the cord on either sid elf the midline and become the anterior (uncrossed) corticospinal tract.
What is involved in voluntary movement?
involves a two-neutron cain between the motor cortex and skeletal muscle. The first neurone has its cell body in the motor/premotor cortex of the frontal lobe and an axon that contributes to the corticospinal tract. These cells are referred to as UMN. upper motor neurones which make up the corticospinal tract extend the full length of the spinal cord and synapse on LMNs.
What is the difference in the symptoms of damage to the corticospinal tract in the brain or brain stem and in the spinal cord?
in brain/brain stem: weakness on opposite side of body
spinal cord: weakness is ipsilateral
What are the two most important somatosensory pathways?
- dorsal column pathway
- spinothalamic tract
What are the similarities between the dorsal column pathway and spinothalamic tract?
- first neuron lies within the dorsal root ganglion
- the second neurone crosses the midline and ascends to the thalamus
- the third neurone lies in the ventral posterior nucleus of the thalamus and project to the primary somatosensory cortex.
The main different is the position of the second neurone and therefore the point of crossing.
What is the dorsal column pathway to do with?
fine, precisely located (or discriminative) touch, joint position sense, proprioception and vibration sense.
Where does the dorsal column pathway originate form?
from low threshold mechanoreceptors and nerve impulses are transmitted to the brain via large diameter fibres that are thickly-myelinated and have high conduction velocities of up to 120m/s
How is the dorsal column pathway best tested?
using a high amplitude, low frequency thing fork applied to bony prominences
What is the spinothalamic tract to do with?
- pain and temperature sensation
- usually tested using sterile neurological examination pins or volatile spray producing a cold sensation
Where does the spinothalamic tract originate?
from nociceptors and thermoreceptros. Pain and temperature impulses are transmitted to the brain via thinly-myelinated A-delta fibres and unmyelinated c-fibres, both of which are of comparatively small diameter and have relatively slow conduction velocities.
What is neurylation?
The folding of the neural plate into neural tube. This process is triggered by growth factors released from notochord.
How does the neural tube begin?
Begins as a single layer of neuroepithelial cells which divide symmetrically to increase in number, and then asymmetrically forming neuroblasts which can migrate.
This is triggered by MCPH1
What is the growth of the neural tube dependent on?
The type of growth is dependent on the morphogen gradient:
BMP, wnt - dorsal aspect of developing brain
Sonic hedgehog - ventral brain
Where they are in the neural tube triggers the chemical signals around and determines what they will become eventually.
This is all dependent on chemical guidance signals.
What are example of chemical guidance signals in the neural tube?
Reelin: outwards - produced in marginal zone
Neuregulins: dorsally
Semaphorin slits: ventrally
How are the cells laid down in the neural tube?
in an inside out fashion - the layer build up from the inside out. This is controlled by changing chemical signals.
what determines the way that axons grow?
Our neuritis need to fid connection. The growth cone consists of lamellopodia and filopodia. These grow in relation to positive/negative (attractive/repulsive) signals.
The axons travel according to signalling proteins via way points.
What happen in synaptogenesis?
- axons look for potentially useful cells
- relies on complementary adhesion molecules
- this triggers the formation of pre- and post-synaptic structures –> IMMATURE SYNAPSE (e.g. neurexin and neuroligin)
what happens if surface molecules in synaptogenesis are not complementary?
When the surface molecules are not complementary, the connection fails. The filopodia retract as a result - e.g. alpha motor neurones and antagonist muscles
What is the function of specific pathways (as opposed to modulatory pathways)?
sensory, motor, cognitive ‘processing’
What is the function of modulatory pathways?
controls the state of the system
What are the types of neural responses in specific pathways (as opposed to modulatory pathways)?
highly specific, event-related, information rich
What are the types of neural responses in modulatory pathways?
non-specific, linked to sleep-wake cycle, behavioural state
What is the synaptic transmission like in specific pathways?
fast, time dependent
What is the synaptic transmission like in modulatory pathways?
slow, imprecisely timed
What is the primary receptor type in specific pathways?
ionotropic
What is the primary receptor type in modulatory pathways?
metabotropic
What is the anatomy of specific pathways like?
precisely located (e.g. topographic)
What is the anatomy of modulatory pathways like?
diffuse
What happens in sleep-wake cycles?
- the thalamus relays information to the cortex
- when we are awake, sensory information is relayed to the cortex, via the thalamus.
- inputs are ignored when we are asleep - due to the inhibitory interneurone –> the cortex instead received synchronised information - regular impulses are put into it.
What happens during REM?
during REM, the thalamus doesn’t follow a typical sleep pattern. the brain changes a bit so an EEG becomes more random - the brain is making up its own sensory inputs.
During REM sleep the muscles become paralysed and this is when you dream.
What happens when someone has an REM disorder?
Their muscles don’t become paralysed and so they enact their dreams.
About Acetylcholine?
- one of the first NTs described
- roles in ANS and PNS
- in CNS; 2 long axon projections:
- -> pontomesencephalic tegmenjtum: thalamus
- -> Basal forebrain: neocortex and hippocampus
About serotonin?
aka 5-HT
- indolamine
- appetite, mood, sleep, aggression
- 2 pathways: rostral group-away from brain, caudal group-towards brain
About norepherine?
- attention and arousal
- ANS - fight/flight
- multiple systems
- be aware of the locus coeruleus system
- projects diffusely
- alertness, increased responsiveness, memory
- defects can cause anxiety
About dopamine?
2 pathways:
NIGROSTRIATAL PATHWAY: projection to the basal ganglia, initiation of voluntary movement
MESOLIMBIC PATHWAY: ventral tegmentum, projects to amygdala and ventral striatum - wakefulness, reward and reinforcement
What can happen as a result of defective mesolimbic pathway?
schizophrenia
About histamine?
- projects to thalamus and cortex
- excites wake promoting cycles
What is falling asleep associated with?
Increased GABAergic activity
What happens as a result of suppression of the modulatory systems?
circadian rhythm, tiredness –> adenosine build up, illness
What increased during REM sleep?
There is an increase in activity from the pontomesencephalic tegmentum - desynchronising thalamic cells
About the frontal lobe…
- primary motor cortex
- contains BROCAS AREA - production of speech
- PREFRONTAL REGION: dorsolateral-executive function, orbitofrontal-personality, social behaviour
What is Broca’s aphasia?
- reduced verbal output
- difficulty in speech
About the parietal lobe…
- the post central gyrus contains the primary somatosensory cortex
- DOMINANT: goal directed movement
- NON-DOMINANT: understand special relations
About the occipital lobe…
- primary visual cortex
- V1: hemianopia
- V2, V3: akinetopsia, achromatopsia
About the temporal lobe…
- primary auditory cortex: hearing
- contains Wernicke’s area: language comprehension
What is Wernicke’s aphasia?
fluent, non-sensical, meaningless speech
What is included in the limbic system?
hippocampus
amygdala
anterior thalamic nuclei
limbic cortex
About the hippocampus…
- knowing where you are/navigations (taxi driver)
- bilateral damage causes profound anterograde amnesia - can’t form new memories
About the amygdala…
- evaluates significance of events
- detects anger
- facilitates social interactions
- learning and memory
Input: cortical inputs, olfactory inputs
Output: toward hypothalamus (efferent) initiates response in ANS ‘FFF’
What can defects in the amygdala cause?
- anxiety
- phobias
- depression
- autism
- epilepsy
- schizophrenia
What is the limbic lobe concerned with?
motivation, mood and memory
What does the limbic lobe include?
cingulate and parahippocampal gyri
Lesions of what can impair memory formation?
cingulate gyrus
What are the responses to stimulation of the limbic lobe?
stimulation of the anterior aspect: painful response, pupils dilate, CV changes
stimulation of posterior: emotional content of visual and tactile sensations
What is controlled by the corticospinal system?
trunk and limb muscles
What is controlled by the corticobulbar system?
head and neck (mouth and throat) - speaking and swallowing
What are the corticospinal and corticobulbar tracts known as collectively and where do they originate?
pyramidal tracts
they originate in the cerebral cortex and carry motor signals to the spinal cord and brain stem
What does the corticospinal tract control?
skilled, voluntary movements
What does damage to the corticospinal tract cause?
contralateral paralysis or weakness (contralateral because it crosses over)
Where does the corticospinal tract originate?
the primary motor cortex, infront of the central sulcus
What is the pathways of the corticospinal tract?
pre central gyrus
corona radiate
internal capsule (posterior limb)
enters the crus cerebra of midbrain and passes through ventral portion of pons
subtotal decussation to caudal medulla and oblongata
lateral and anterior corticospinal tracts
Which sides of the body to upper motor neurone lesions affect?
Above the motor decussation: opposite side affected
Below the motor decussation: same side affected
What is the cerebellum responsible for?
planning movements as well as execution
compares the movements planned with those actually carried out
What are the motor advisors?
The basal ganglia and the cerebellum
What is the comparison done in the cerebellum known as?
feed forward comparator
Where does feedback come from to the cerebellum?
ear, eyes, vestibular nuclei, proprioceptors
What is the feed forward comparator?
cerebellum takes in all the feedback and modifies the action the second time
What is the spinocerebellum responsible for?
regulating muscle tone and posture
What is the cerebrocerebellum responsible for?
high level planning movements, cognitive functions - pontine nuclei afferents and BL thalamus efferents
What is the vestibulocerebellum responsible for?
maintaining balance and eye movements
What kind of neurones are lower motor neurones?
second order neurones
What are symptoms of UMN lesions?
- pyramidal weakness
- no wasting of muscles
- spasticity, clasp knife response, clonus
- hyperreflexia
- positive Babinski reflex, extensor planter response
- absent abdominal relfexes
What are the symptoms of LMN lesions?
- weakness (paralysis or paresis)
- wasting of individual muscles
- hyporeflexia
- hypotonic or flaccidity
- fasciculations
What is proprioception?
the sense of the relative position of neighbouring parts of the body - including rate and trajectory of body movements
What are the two types of muscle spindle fibres?
Type Ia afferents associated with nuclear bag fibres –> encode velocity of stretch
Type 2 afferents - associated with nuclear chain fibres –> encode length of muscle
What is the difference in contractility of extrafusal and intrafusal muscle fibres?
extrafusal muscles contract
intrafusal muscles have contractile edges innervated by gamma motor neurones, but the middle portion is elastic not contractile.
The afferents fire when they are stretched in the middle.
What happens in the muscle fibres during voluntary movement?
- alpha motor neurones fire when voluntary movements occur
- gamma motor neurones simultaneously fire keeping the middle bit taught and unchanged as both contract a corresponding amount
What happens in the muscle fibres in involuntary movement?
afferent firing activating alpha motor neurones so contracts more and get more stretch - e.g. muscle more stretched than expected when something is heavier than you thought
this is the stretch reflex
What is the role of muscle spindles?
if the muscle is voluntarily stretched - central portion unchanged = no excitatory activity. Descending control systems also inhibit contraction so that the muscle doesn’t resist stretching.
Posture - if the muscle contracts too little to overcome gravity - central portion is stretched and the muscle contracts more.
if an unexpected load causes a movement to be inaccurate, same process as above takes place
What are the two types of inhibition (proprioceptors)?
- reciprocal inhibition
- presynaptic inhibition
What is reciprocal inhibition (proprioceptors)?
antagonist motor neurone inhibited by Ia afferent of contracting muscle
What is presynaptic inhibition (proprioceptors)>
contracting Ia afferent inhibits release of NT from antagonist Ia afferent (so there is no stretch in the antagonist muscle)
eg as soon as afferent fires saying bicep is contracting, inhibitory efferent will stop the triceps contracting at the same time
What is an UMN lesion?
anywhere between cell body and LMN causing loss of regulation of reflexes and conscious control
What is an LMN lesion?
the alpha motor neurone lesion causes loss of innervation to muscle
What is the role of golgi tendon organs?
measure tension generated by contraction (stretching doesn’t usually cause much tension)
they are within the tendon
What states does the UMN control whether the muscle is in?
inhibited: static situations
excited: dynamic situations
When do afferents fire in relation to golgi tendon organs?
when the tendon squeezes - when these fire there are UMN and upper control systems that decide what happens - they can either activate an excitatory pathway or an inhibitory pathway
What is an example of a dynamic situation (golgi tendon organs)?
Walking
What is an example of a static situation (golgi tendon organs)?
standing still
what might the loss of the golgi tendon organ pathway cause?
weakness in gait, or hypotonia - can’t stand still
What are possible types of injury in the CNS?
- developmental
- trauma
- ischaemic
- hypoxic
- inflammatory
- neurodegenerative
- infection
- tumours
What is a direct response to brain injury?
inflammation and oedema
About stroke…
- acute loss of blood supply damages the region supplied by the blocked artery
- it takes 6-8 minutes of blood supply interruption (ischaemia) to cause neuronal cell death (infarction)
- most cerebral vascular occlusions will reopen spontaneously within 24 hours, but for the neurones this is too late
- during this time it has been calculated you lose 2 million neurones per minute
What is hypoxic brain injury?
reduction of whole brain oxygenation - preferentially affects the most metabolically active parts of the brain –> grey matter: cerebral cortex, basal ganglia
What is the series of events in multiple sclerosis?
inflammation
demyelination
neuronal dysfunction
What happens as a consequence of axon death?
- upstream: the cell body may die via apoptosis (retrograde degeneration)
- downstream: the distal axon dies via Wallerian degeneration (anterograde degeneration)
What are the consequences of denervation for the target neurone?
- from subtle changes e.g. transmitter hypersensitities in spinal cord injury resulting in spasticity
- to transneuronal atrophy or degeneration eg visual and auditory systems
What is meant by anterograde?
directed forwards in time
What is the definition of retrograde?
Directed or moving backwards
What is retrograde degeneration?
- depending on site there may be rapid degeneration of the projecting neurone
- eg cortical stroke leads to rapid degeneration of thalamic neurone that project to the cortex
What are mechanisms of spontaneous recovery in the CS?
- glial scarring
- neurogenesis
- regeneration
What is glial scarring?
- glial scar formation (gliosis) is a reactive cellular process involving proliferation of astrocytes and microglia after injury to the CNS
- this is a mechanism to protect any part of the healing process
- in the context of neuronal injury however, formation of a glial scar has been shown to have both beneficial and detrimental effects
- regenerates a tissue barrier after blood-brain barrier compromise and promotes revascularisation of injured brain
- in particular, neuro-developmental inhibitors are secreted by astrocytes that prevent axon regrowth and regeneration
What is neurogenesis?
- the birth of new neurones
- nervous system could repair itself if it could grow new neurones
- occurs in many non-mammalian vertebrates e.g. amphibians, songbirds
Where is there evidence for significant neurogenesis?
- hippocampus (dentate gyrus)
near the lateral ventricles (subventricular zone), supplying the olfactory bulb - both important for memory, so perhaps memory does’ grow’
What happens in regeneration?
- regrowth of severed axons
- occurs in non-mammalian vertebrates
- occurs effectively in mammals peripheral nervous system only
Why is myelin critically important (and in regeneration)?
- provides a guide tube for the sprouting end of a severed neurone to grow through
- extending axon guided to its destination during development
What happens with regeneration in the human CNS?
- true regeneration of axonal projections rare
- developmental loss of regenerative ability –> down regulation of growth related genes
- due to micro environment –> trophic factors vs inhibitory factors –> glial scars - chemical/physical barrier
What are treatments that can modulate recovery of incurable neurological diseases?
Neurorehabilitation: the clinical specialty that is devoted to the restoration and maximisation of functions that has been lost due to nervous system injury from whatever cause
capitalises the way the brain normally learns to relearn lost function
What is neural plasticity?
the ability of the brain to change structurally and functionally as a result of input from the environment
- this is a normal phenomenon underlying brain function
- reorganisation of neuronal processes resulting in functional and structural rearrangement
- widespread: sensory, motor, visual, language systems at all levels of neuroaxis
- plasticity occurs on a variety of levels, ranging from cellular changes due to learning, to large scale changes involved in cortical remapping in response to injury
What is somatotopy?
point-for-point correspondence of an area of the body to a specific point in the CNS.
What do discrete areas of the cortex do?
- control motion of specific small groups of muscles
- receive sensation from specific areas of the body
- subserve vision from specific areas of the visual field
- subserve audition for specific pitches of sound
Are specific area son the brain specific to certain functions?
- functions are also shared and to an extent degenerate
- flexible and subject to neural plasticity - can be changed by:
peripheral and central injury
electrical stimulation
learning and experience - eg cortical representation of left hand finger movements is expanded in violinists –> the homunculus is not fixed
How do you fix the brain is you can’t grow new neurones?
- COMPENSATION: having one brain area take over the functions damaged in another area, simple neural recovery: uninjured tissue takes over functions of lost neurones
- presynaptic neurons sprout more terminals: form additional synapses with their targets and postsynaptic neurones, also add more receptor cells
- REORGANISATION: a more dramatic form of neural recovery, can involve major brain areas
What is reorganisation of neurones?
stimulation continues to shape synaptic construction and reconstruction throughout the individuals life –> experience is critical
- a shift in connections that changes the function of an area of the brain
- much of the change resulting from experience in the mature brain involves reorganisation
- in some cases (not all) can lead to cortical remapping
What are examples of neural plasticity after brain injury?
- hemispherectomy in young children: outcome can be surprisingly good, language reorganisation and relative intellectual preservation
- in deaf people portions of visual cortex may be used for reading braille and other non-visual function
- recovery of function after stroke
What are putative mechanisms?
Neural plasticity can be expressed as activity dependent modifications int eh efficacy of existing synapses:
- unmasking (removal) of inhibitory pathways
- long term potentiation
- synaptogenesis
Briefly about adult stem cells?
- pluripotent
- limited tissues (bone marrow, muscle, brain)
- -> discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury or disease
- umbilical cord/placenta
What are the ‘bystander’ effects of stem cell transplantation?
- intrinsically neuroprotective
- anti-inflammatory
- delivery of trophic factors
- overcome natural inhibitors
What is the CPG?
responsible for the collection of neurones which makes movements happy. This is all controlled by the spinal cord and doesn’t require the brain.
What happens if you lose the anterior horn cell?
you are paralysed as it is the final connection to the muscle
About the phrenic nucleus…
supplied phrenic nerve
- C3, C4, C5
- supplies diaphragm
- breathing
About the spinal accessory nucleus…
up into skull and back down
- C5, C6
- supplies sternocleidomastoid, trapezius
- head turning, shoulder shrugging
About Onus’s nucleus…
sacral canal, where parasympathetic fibres come out
- S2, S3, S4
- supplied external urethral and anal sphincters
- continence
What does the amount of grey matter in the spinal cord depend on?
muscle bulk at that level
i.e. there is lots at the locations of the arms and legs, less as you go down
What types of movements are there?
- reflexes: stereotypes (automatic, simple reflex arcs, triggered by proprioceptors)
- rhythmic movements: breathing, walking, sometimes automatic sometimes voluntary (semi-automatic, involving brain stem and spinal cord. Do not necessarily require attention, can be controlled voluntarily)
- voluntary actions: motor neurone direct connection form spinal cord, corticospinal tract (least automatic, e.g. writing, playing piano, speaking, goal-directed, dependent upon cerebral cortex)
What is the flexor/withdrawal reflex?
- polysynaptic (several segments)
- cutaneous reflex
- elicits limb withdrawal
- triggered by nociceptors
- leads to limb flexion
What is the crossed extensor reflex?
- triggered at the same time
- causes contralateral limb extension
- supports body weight
eg stand on a pin and pull one leg away but straighten the other to support weight
How is an action potential reached in the sensory system?
- external event/stimulus
- sensory receptor cell detects and converts the energy in the stimulus into an electrical potential (transduce)
- depolarisation of membrane
- if gets afferent up to threshold
- action potential
What are possible answers to damaged/lost receptors (e.g. hearing)?
- transplantation of surviving receptors
- production of new receptors from stem cells
- gene therapy to make other retinal cells photosensitive
What allows for one detail/discriminative touch?
receptive fields which are very small and close together, allowing the brain to reconstruct the afferent of the singles sent on the brain pad.
if you have a small receptive field then you need lots of afferents to innervate that field - small receptive field require high innervation density
Why is temporal resolution limited?
spatial resolution is limited, temporal resolution is limited. the two signals produce tapping in one little area right on top of each other and will probably feel like a single tap.
what is the action potential threshold?
the membrane potential at which action potentials are triggered. this is a function of the vgNa+ channel and can be treated as a constant
What is the ‘activation’ threshold?
the minimum stimulus strength that will depolarise a receptor enough to generate action potentials. sensory systems use receptors with a range of different activation thresholds.
What is ‘perceptual’ threshold?
the minimum stimulus strength that will generate enough action potentials to be detected.
perceptual threshold is the bit we can most easily test in a clinical environment
this is the limit that someone can reliably detect the stimulus - this will change depending on how long the subject is attending to the stimulus - if they get bored it will shrink
