Motor Control and Disease 1 & 2 Flashcards
all movements produced by skeletal musculature are initiated by …
lower motor neurons
spinal cord contains central pattern generators that can generate complex behaviour without input from brain
but several subsystems in braininfluence these behaviours
stimulation of motor cortex elicits muscle movement
shown on dog that electrical stimulation of part of the cortex elicits contraction f contralateral body muscles
region became known as (primary) motor cortex
neurons found in brain that control motor function are called upper motor neurons
motor cortex is also somatotopically mapped
correlated site of stimulation with location of muscle contraction and made topographic map
not identical to somatosensory map
but lower body is still medially represented and upper body - laterally
somatic motor system basics
control of lower motor neruons in ventral horn of spinal cord which innverate straited muscle to control movement
speficially:
axial muscles - trunk movement
proximal muscles - shoulder, elbow, pelvis, knee movement
distal muscles - hands, feet, digit movement
innveration via specialised synapse = NMJ
lower motor neurons
each muscle fibre receives input from a single lower alpha motor neuron
each lower motor neuron innverates the fibres of one muscle
motor unit
motor neuron and all muscle fibres it innverates
motor neuron pool
all the motor neurons that innverate a single muscle
motor pools are spatially organised in spinal cord
motor pools are grouped in rod shaped clusters within spinal cord extending over several vertebral segments:
we know from experiments in animals where tracers were injected into specific muscles, which were then transported back along the motor axons to the cell bodies in spinal cord
- injection in gastrocnemius, labels a different set of motor neuron cell bodies to injection of soleus
motor pool organisation is somatotopic
the medio laterl position of a motor pool reflects whether its motor neurons innverate a proximal or distal muscle
therefore motor pools are organised somatotopically both medio-laterally and rostro-caudally
i.e. there is a 3D map of the bodys musculature within the spinal cord
somatotopy in motor cortex ….
reflects location of upper motor neurons that innverate lower motor neurons in spinal cord
lower motor neurons receive inputs from local souces in spinal cord, but also directly from upper motor neurons
upper motor neurons project axons to lower motor neurons via descending tracts of spinal cord
corticospinal tract is key for control of voluntary movement, one of the lateral pathways of spinal cord
axons of certicospinal tract originate in layer 5 of motor cortex
pyramidal cells of motor cortex project axons in CST
90% of cortex, including motor cortex, is a 6 layered structure
main inputs are to stellate cells in layer 4
main outputs are from layers 3, 5 and 6
axons of CST derive from large pyramidal cells (Betz cells) in layer 5
different sets of upper motor neurons control different functions
CST outputs to upper body originate from lateral motor cortex and outputs to lower body = medial motor cortex
axons of CST then cross midline in pyramidal decussation in medulla, they project laterally in spinal cord, synapse on laterally located lower motor neuron circuits that control distal muscles (especially at limb levels)
the CST is one of lateral pathways
upper motor neurons in brainstem
they project to medial motor pools primarily concerned with postural movement
axons from brainstem project ipsilaterally in several tracts e.g. vestibulospinal and reticulospinal
project medially in spinal cord
synapse on medially locatde lower motor neuron circuits that control axial muscles
these are the ventromedial pathways
motor cortex upper motor neurons ….
primarly concerned with fine voluntary control of distal structures
ventromedial pathways control …
posture
vestibulospinal tract - head balance and turning (inputs from vestibular system)
tectospinal tract - orienting response (inputs from visual system via superior colliculus)
reticulospinal tracts - control antigravity reflexes
project mainly ipsilaterally and medially
upper motor neuron control recap:
motor cortex
initiate complex voluntary movements
project mainly contra laterally via CST, primarily to muscles involved in precise limb movements - particularly hands in humans, lateral pathway of spinal cord
also project via corticobulbar tract to hypoglossal nucleus in brainstem - controls tongue movement
upper motor neuron control recap:
brainstem
maintenace and balance in several nuclei including - reticular formation - vestibular nucleus - superior colliculus project ipsilaterally to lower motor neurons controlling axial muscles concerned with maintiang posture - the ventromedial pathways of spinal cord
upper motor neurons always ….
synapse on lower motor neurons, or their interneuron circuitry
lower motor neurons always ….
synapse directly in muscle fibres
integration of postural control with voluntary movement
volunteer lifts lever in response to audio tone
recording from different muscles reveals the first to contract are in leg
= anticipatory ‘feedforward’ mechanism, pre adjusts body posture to compensate for forces that will be generated when lever is lifted
indirect cortical control of lower motor neurons
feedforward mechanism makes sense when you realise that upper motor neurons in cortex influence spinal cord circuits by 2 routes:
area 6
area 4
area 6 control
movement anticipation starts in premotor area (PMA)
activates an indirect projection to axial muscles via reticular formation
area 4
movement initiation then happens in primary motor cortex (M1)
activation of voluntary movement direct to spinal cord via corticospinal tract
activity in PMA preceeds activity in M1 and coincides with movement planning/anticipation
so anticipation involves …
a circuit from motor cortex to brainstem nuclei
motor cortex innverates both brainstem and spinal cord
motor neuron disease
MND/ALS
degenerative disease of motor neurons
characterised by muscle atrophy and sclerosis (hardening or scarring) of lateral spinal cord, which is the mark of degeneration of axons is CST
motor neuron disease - neuropathy and etiology
can affect both upper and lower motor neurons
one of several neurodegenerative diseases
what causes neurons to die is not understood
excitoxicity maybe a possibilty - overstimulation, typically by glutamate, leads to neuronal cell death
vicious cycle if glutamate can occur, particularly in hypoxic condition e.g. after cardiac arrest, stoke
only drug to have any effect = blocker of glutamate release (riluzole) but only delays disease by months
10% ahve clear genetic basis
one results from mutation in gene coding for superoxide dismutase, key enzyme that ‘mops up’ free radicals that accumulate in metabolically active cells
lower motor neuron disease
characterised by:
muscle paresis/paralysis
loss of muscle tone due to loss of stretch reflexes
leads to severe muscle atrophy (loss of muscle mass)
patients usually die from lung dysfunction - due to atrophy of intercostal muscles
upper motor neuron disease
characterised by:
muscle weakness
spasticity due to increased muscle tone (due to failure of modulation of stretch reflex
hyperactive reflexes
loss of fine voluntary movement
patients usually die from loss of input to bulbar muscles - tongue and pharynx - via corticobulbar tract
basal galnglia and cerebellum
influence movemnt indirectly by regulating function of upper motor neurons - no direct connection to lower motor neurons
basal ganglia and associated structures
key components in initation of movement: motor cortex (telencephalon) basal ganglia - forebrain - caudate - putamen - globus pallidus - subthalmic nucleus ventral lateral nucleus of thalamus (diencephalon) substantia nigra - midbrain
the motor loop
basal ganglia motor cortex connects to the basal ganglia, which in turn feedback to premotor area (area 6) via ventrolateral complex of thalamus to control initiation of movement = motor loop consists of 2 pathways - direct - indirect
basal ganglia
direct pathway
with no initaiating cortical input, globlus pallidus internal segment (GPI) tonically inhibits the ventrolateral complex (VLo)
input from many cortical regions converges on stratum
when activated by this input, the straitum inhibits the inhibitory activity of the GPI, releasing the VLo to activate area 6 and initiate movement
basal ganglia
indirect pathway
direct pathway is modulated by a complex indirect pathway which involves substantia nigra - SN and globus pallidus external segment - GPE
SN has complex role and acts vis striatum to maintain balance between inhibition and activation of VLo
- excitatory input from SN stimulates VLo by activation, by activating the inhibition of the GPI through the direct pathway
- in indirect pathway, inhibition of GPI by GPE is inhibited by striatum and so VLo is inhibited
- however, inhibitory input from SN decreases striatum inhibition of GPE, which then inhibits the GPI allowing activation of VLo
so SN is balancing/turning the activation of VLo
degeneration of neurons in different parts of this circuit leads to Parkinson’s or huntingtons disease
parkinsons disease - incidence and symptoms
2nd most common Neurodegen disorder
sporadic cases = 85-90%
familial cases = 10-15% caused by genetic mutations
caused by loss of dopamine
motor symptoms:
- hyopkinesia - insufficiency of movement
- bradykinesia - very slow movement
- akinesia - no movement
- inc muscle tone - rigidity
- resting tremor
- shuffling gait and flexed posture, impaird balance
- mask-like expression
non motor symptoms = mood disorders, loss of smell
dopamine loss
due to loss of dopaminergic neurons in SN
80% of brains dopamine found in basal ganglia, specifically SN
degeneration of these neurons is marked by presenc of lewy bodies - intracell protein aggregates
L-DOPA
effective but temporary therapy
provides dramatic but brief relief of symptoms intravenously
later found that oral L-DOPA provides longer and more significant benefits
beneficial effects only last for 5 years:
works by boosting capacity of surviving neurons in SN to make dopamine
but does not stop degeneration of SN neurons
eventually there are insufficient SN neurons left to make dopamine
side effects: increase motor response fluctuations and drug related dyskinesias
basal ganglia
effects of loss of dopamine
reduced dopaminergic input from SN to straitum leads to both:
1) increased activity of indirect pathway
and
2) decreased activity of direct pathway
= less inhibition of GPI and so it inhibitory activity is increased
= leads to decreased activity of VLo and so less motor cortex activation
L-DOPA reverses this effect but only as long as DA neurons are present
in severe parkinsons cases, surgical removal of GPI can be effective in reversing effects
but more recently deep brain stimulation is used to inhibit GPI hyperactivity
huntingtons disease
rare, hereditary, fatal
symptoms:
early - hyperkinesia or dyskinesia, ‘chorea’ involuntary jerking or twiching movements
late - akinesia and dsytonia (muscle spasms), dementia, psychosis
cause:
autosomal dominant genetic disease
- initally in indirect pathway components of striatum
- subsequently in direct pathway components and in GPE
basal ganglia
in huntingtons
early on;
degeneration in striatum reduces the indirect pathway inputs to the GPE
this increases the inhibition of the GPI with the result that VLo is dis-inhibited and there is inappropriate initiation of movement - hyperkinesis, chorea
later:
striatal direct path and GPE neurons also degenerate, releasing GPI to over-inhibit the VLo - akinesis
