Download control of movement by the CNS - motor neurons found in anterior

control of movement by the CNS
- motor neurons found in anterior horns
medial column - trunk, lateral column - proximal then distal limbs
- motor unit = motoneuron + all the muscle fibres it innervates
- 3 types of muscle fibres
slow oxidative - slow twitch, low force, lots of myoglobin/mitochondria, non-fatiguing
fast oxidative/glycolytic - moderate twitch, force, etc... fatigues slowly (minutes)
fast glycolytic - fast twitch, large force, little myoglob / mito, fatigues quickly (<1 min)
- the faster the fibre, the larger diameter of the motoneuron that innervates it
smaller neurons more easily excited by summated EPSPs
slow motor units recruited by low levels of synaptic input
fast motor units recruited by high levels of excitatory synaptic input
- one action potential –> one twitch (100-300 ms)
for effective action, need summation of twitches
summation of twitches = tetanic contraction (6-10 imp/s or more)
maximal summation (maximal force output) = fused tetanus (30-40 imp/s)
all this happens because APs are coming so fast Ca can’t be sequestered
- motor units, when first recruited, fire at 6-10 imp/s
fire at faster rates only in brief bursts to increase speed of contraction
- Renshaw cells
inhibitory glycinergic interneurons adjacent to motor nuclei
excited by collateral branches of motoneuron axons (cholinergic input)
provide inhibitory feedback to limit discharge rates to below 35-40 imp/s
- gamma motoneurons
smallest motoneurons, easy to excite, innervate muscle spindle intrafusal fibres
adjust sensitivity of muscle spindle, modifying perception of stretch
- alpha motoneurons
larger motoneurons, innervate extrafusal work-producing fibres
- recruitment
first gamma, then slow, then fast
to increase force: increase m.u. discharge rates, or recruit more (and faster) m.u.’s
- motoneuron bistability
when strongly excited, maintain memb. pot. just below threshold
decays to normal after about 40 s.
useful in maintaining tonic contraction (eg. postural muscles)
- length-tension relationship
maximum tetanic tension produced at a particular muscle length
this corresponds to length where actin and myosin can form the most cross-bridges
longer or shorter lengths produces progressively weaker contractions
- physiological tremor
roughly 10Hz fine tremor observable in outstretched fingers
synchronous discharge in newly recruited motor units (firing at 10 imp/s)
greater tremor with greater synchrony of discharge
- cortical myoclonus
uncontrolled twitching and jerking of limb muscles
drive comes from hyperexcitable cortex (genetic or post-ischemic)
spinal reflexes
- stretch reflex
stimulus: passive stretch by load or antagonist muscle
response: active contraction of muscle
sensory organ: muscle spindle (inside capsule, wrapped around intrafusal fibres)
afferents: Ia - big, fast, sensitive to changes in stretch
II - smaller, slower, sensitive to static stretch
function: postural stabilization, suppressed during movement
- Golgi tendon reflex
stimulus: excessive force in tendon (active tension in muscle)
response: relaxation of muscle
sensory organ: Golgi tendon organ - distorted by force of active contraction
afferents: Ib - slightly slower than Ia, slowly-adapting, synapse on interneurons in
intermediate zone, which inhibit alpha-motoneurons of same muscle
function: prevent movement, control tension, suppressed during movement?
- flexion withdrawal reflex
stimulus: noxious injury of limb
response: flex joints proximal to stimulus, extend distal joints
sensory organ: ?
afferents: A, C nociceptor - small diameter, slow, multisynaptic path (interneurons),
commissural interneurons carry signal for contralateral extension
function: avoid bad things
- reciprocal inhibition
basic property of intermediate zone
eg. activation of flexors elicits inhibition of extensors
suppressed when co-contraction is desired (ie. for joint stiffness)
- Babinski sign
extensor thrust reflex (in foot) influenced by corticospinal tract
if this is damaged, reflex pattern switched to flexion withdrawal
- presynaptic inhibition
main mechanism for regulating and switching reflex afferents
when one route to a motor nucleus is inhibited, another can be disinhibited
acts via... glycine or GABA or depolarization?
- reflex adaptation
can be rerouted via a different pathway (eg. Babinski)
can adjust gain (output per unit input)
- Hoffman reflex
peripheral nerves have both afferent and efferent fibres
stimulate one nerve, get two muscle responses
faster M-wave due to stimulation of motor neuron
slower H-wave due to stimulation of Ia afferents (reflex arc)
for an increasing stimulus, get H-wave first (25V) then M-wave (40V)
further increase, M-wave increases but H-wave decreases (60-90V)
due to: refractory motoneurons, Renshaw inhibition, more Ib inhibition?
orthodromic activity in sensory neuron collides with antidromic activity in
motoneuron
posture
- types of postural activity
tonic maintenance of ‘antigravity’ body configuration
stabilization during movement - skeletal support, mechanical, centre of gravity shift
(every limb movement requires ‘anticipatory postural adjustment’ in rest of body)
- postural maintenance
organized in reticular formation (pons and medulla)
3 sensory sources: somatosensory (esp. proprioceptive), vestibular, visual
- proprioceptive reflexes
stretch and tendon reflexes stabilize joints, but narrow operating range
large perturbation -> ‘automatic postural reaction’ (programmed response, not reflex)
eg. decerebrate cate with labyrinths removed (head up -> sit, head down -> crouch)
- vestibulospinal reflex
stimulus: downward deviation of head to one side
response: ‘downhill’ limbs extend
afferents: otolith afferents -> lateral vestibulospinal tract -> ipsilateral extensors
function: maintain upright posture
- vestibulocollic reflex
afferents: semicircular canal and otolith afferents to vestibular nucleus
efferents: medial vestibular nuclei -> neck motor nuclei
function: stabilize head w.r.t. trunk (eg. while walking)
- vestibulo-ocular reflex
stimulus: head rotation
response: compensatory eye movement
afferents: semicircular canal afferents
efferents: superior vestibular nucleus -> MLF -> extraocular muscles
- visual postural reflexes
low effect, operates at low frequencies (<0.3 Hz)?
complement to vestibular reflexes which respond to higher frequencies
align body axis with visual perception of vertical
- automatic postural reaction
centrally programmed response to restore grossly perturbed centre of gravity
subjugates local reflexes, coordinates action across entire body
organized within reticular formation of medulla and pons
- sensory substitutions
closing eyes doubles postural sway, compensated by lightly touching stable surface
visual and somatosensory inputs constantly reweighted according to congruence with
vestibular (gravitational) reference
persistant visual / vestibular incongruence can lead to motion sickness
- red nucleus
midbrain centre for discrete distal synergies, not part of posture / locomotion
rubrospinal tract projects to contralateral intermediate zone and motor nuclei
probably responsible for most basic hand movements in humans
- synergy
group of muscles contracting together for a specific purpose
reticulospinal synergies are very widespread (eg. for support postures)
rubrospinal (and corticospinal) synergies are highly localized
- decerebrate rigidity
brainstem transection b/w vestibular complex and red nucleus
net increase in reticulospinal activity -> extensor stretch reflexes facilitated
higher centres (red nucleus, motor cortex) normally suppress postural drive
- reticular activating system
cholinergic - control of posture and goal-directed movements
controls corical excitability - EEG changes
affective changes to sensory stimuli esp. pain - changes in sleep/wake cycle
motor control of ‘vital reflexes’: circulation, respiration, swallow, cough
- brainstem stroke
contralateral involvement of body, ipsilateral involvement of face
medial medullary syndrome: ipsilateral paresis, atrophy and fibrillation of tongue,
contralateral hemiplegia sparing the face, contralateral loss of position and vibration
central pattern generator
- reflexes vs. central pattern generation
opposing reflexes can create alternating action through sensory feedback
eg. 1914 “Reciprocal inhibition underlies rhythmic behaviour of walking -- sensory
basis of reflexes underlies rhythmic movements”
CPG creates ocillation without sensory feedback
eg. 1960's - deafferented locust flight produces fictive motor patterns in the absence
of all sensory input
- effects of deafferentation on locust flight
cycle frequency decreases due to increased depressor-elevator interval
- CPG behaviour depends on intrinsic membrane properties of cells
endogenous bursting cells - timing inputs
plateau potential cells (start with depol, stop with hyperpol) - memory, tonic drive
postinhibitory rebound - synchronize CPGs
spike freq. adaptation during constant depol.
- mechanisms of rhythm generation
pacemaker - eg. vertebrate breathing
reciprocal inhibition / half-centre oscillators - eg. lamprey swimming
not just network wiring, but also different properties of individual cells
types of coupling: pacemaker/follower vs. reciprocal inhibition
- lamprey locomotor network
E-interneurons excite all ipsi I, L, M neurons
I- interneurons inhibit all contra I, L, M neurons
stretch receptors (SR) excite ipsi and inhibit contra
reticulospinal (RS) neurons receive all sensory and higher input, excite all spinal stuff
- sensory control of CPG
adaption to imposed movements
sensory (stretch) input matches CPG rate to rate of imposed movements
- spike frequency regulation
large slow afterhyperpolarization (sAHP) means fewer spikes in burst
Ca dependent K channels cause sAHP and terminate NMDA plateau potentials
many factors determine burst onset and end:
NMDAR, low voltage Ca channels
stretch receptors start (excitatory) and stop (inhibitory) the burst
synaptic excitation from excitatory neurons (ie. reticulospinal neurons?)
- visuo-vestibular control of lamprey “roll-control”
like extensor motor reflex
vestibular input excites contra eyes and ipsi reticulospinal neurons
response is corrected motor roll
- synaptic modulation
postsynaptic metabotropic glutamate receptors mediate RS –> increased freq of CPG
postsynaptic Group I do that... presynaptic Group II and III can inhibit glu release
- vertebrate models of CPGs
spinal cord much more complex
CPG involved in locomotion, breathing, etc.
half-centre organization found in cat spinal cord
human central CPG - maybe involving STN and GP (eg. Parkinsonian tremor)
- significance of all this
spinal cord recovery may benefit from activation of CPGs below lesion site
electrical stim, pharm. tx, weight-bearing treadmill training... can enhance recovery
cortical motor control
- motor cortex
large layer 5 pyramidal cells (Betz cells) project via corticospinal/bulbar tracts
direct synapses on motoneurons mostly to distal limb and speech motor nuclei
premotor (area 6), motor (area 4), posterior parietal (areas 5 and 7)
somatotopic organization... regional ‘concentric’ plan around distal foci (fingers, toes)
- distal-axial gradient
distal muscles tend to be deep in central sulcus while axial closer to premotor cortex
- multiple representation
single motor nuclei represented by columns of neurons at many loci
each cortial locus represents a different synergy
muscles participating in the most synergies have biggest representation
- cortical column
functional unit of cortex
about 1mm across, goes through all layers
stimulation anywhere in column gives same motor response
- motor cortex maps synergies
cells in one column may fire when muscle is active in a specific movement (synergy)
same cells may be silent when same muscle participates in a different movement
not necessary to represent every possible muscle synergy
finite set of cardinal synergies, which can be combined and weighted
- coding direction of reach
many cortical columns contribute to generation of reach
each will be active for reaches over a range of directions
one direction coded by ratio of activity across the pop. of neurons (population coding)
- somatosensory inputs
only sensory input with direct access to motor cortex
cutaneous input from somatosensory association areas, related to posture and motion
proprioceptive input direct from thalamus (and form somatic assoc. cortex)
- transcortical reflexes
stretch reflex - same as spinal reflex but longer latency and more modifiable
proprioceptive signals from one muscle trigger contractions in others
helps to syncronize actions at several joints
eg. grasp reflex
slipping object in fingers activates mechanoreceptors
direction of slip computed in somatosensory association areas
increased finger tension triggered in motor cortex
- stroke
eg. cerebrovascular infarct deep in white matter or interal capsule
both corticobulbar and corticospinal tracts damaged
corticospinal - muscle weakness or paresis
corticobulbar - spasticity
- spasticity
hyperactive spinal stretch reflexes (velocity sensitive)
excessive resistance to passive stretch of muscles
- premotor areas
set of regions projecting into motor cortex, but also to brainstem and spinal cord
select motor cortical synergies in proper sequence
preparatory role: coordinate postural support and focal limb movements
- postural integration
every cortical movement must be supported by ‘anticipatory postural adjustments’
postural programs in brainstem reticular formation are activated or suppressed by
premotor cortex, in parallel with motor cortical activation
- preparatory activity
related to ‘working memory’.. premotor neurons often inactive during actual movement
active during prep: selecting appropriate cortical and postural synergies
- motor field
one corticospinal axon synapses with a set of motor nuclei (>1 spinal segment)
set of muscles influenced constitutes the motor field
weighting of synaptic strength: some nuclei influenced more than others (some silent)
- cortical plasticity
representation fo muscles in motor cortex changes with use
sustained vigorous activity in one column leads to expansion into adjacent territory
sustained somatosensory inputs to motor cortex increase their synaptic influence
(long-term potentiation)
- premotor areas
cingulate motor area (CMA): 2 representations of body within cingulate sulcus
supplementary motor area (SMA)
premotor cortex: dorsal and ventral parts
Broca’s area: ventral premotor cortex in left hemisphere
- supplementary motor area (SMA)
on medial wall of hemisphere
somatotopic representation of body, less detail than motor cortex
processes internal ‘volitional’ signals that drive movements
controls bilateral coordination of limbs when diff. motions done on each side
- cingulate motor area (CMA)
gross somatotopic representation within cingulate sulcus
processes emotional and motivational drive to movements
‘limbic motor center’, important in many epileptic seizures
also contributes to corticospinal tract
- lateral-medial differences
medial premotor zones (SMA, CMA) process internal, volitional drives to move
lateral premotor zones process sensory drives to move (learned sensory cues)
eg. door knob, sound of boss’ footsteps, etc
each premotor locus processes different kinds fo information
- premotor cortex
processes sensory inputs, esp. visual and auditory, for cueing movement phases
activates cortical synergies in proper sequence
many loci in premotor cortex project to same motor cortical synergies
dorsal vs. ventral portion?
- ventral premotor cortex
Broca’s areas - organizes sequences of phonemes for speech, hand movement
sequences fo writing
‘mirror neurons’ found in this zone
stroke here may result in aphasia - can’t synthesize grammatical/coherent phrases
input from Wernicke’s area
- mirror neurons
elicit specific movement in motor cortex eg. hand gesture
receive parietal postural info and temporal lobe visual discrimination of the gesture
neuron activated by the sight of someone else performing the gesture
- reach and grasp
frontal motor areas need to know:
current position of arm and hand
location of target object relative to hand
shape and orientation of object
all this comes from neurons in parietal and temporal lobes
parietal lesion: misdirection of arm, lack of hand pre-shaping
- parietal cortex
representation of body image, specific limb posture (eg. hand configuration)
in post. parietal lobe, neurons either respond to spatial location of targets w.r.t hand,
or to shape of objects that match a specific hand posture
needed for spatial guidance, hand shaping
- lateralization
R side parietal lesion can result in left-sided hemineglect
L side lesion can cause ideomotor apraxia (problem with purposeful movements)
- due to disruption of path b/w ideation centre and motor centre
(memories for skilled movements found in left angular gyrus)
left frontal (Broca’s) area for speech, right side for prosody (rhythm and tone)
- alien hand syndrome
lesion in medial premotor/prefrontal region
loss of volitional inhibitory control over sensorimotor loops in lateral frontal lobe
sensory drives free to elicit movements without willed ‘permission’
cerebellum
- role in motor system
not essential... agenesis -> delayed motor devel, perpetual clumsiness
cerebellum is ‘conductor’ of motor system, doesn’t generate any actual movements
- structure
cortex - receives most of input
nuclei - provide excitatory output to motor centres
cortex inhibits deep nuclei via Purkinje cells (GABA)
- cortex (input)
3 layers: granular, Purkinje, molecular
granule cells receive input from mossy fibres
(spinal cord, brainstem, cortex, sensory (dynamic), and motor signals)
each input projects to a region, but lots of overlap and mixing
project axons up to molecular region, then form parallel fibres to interact /w Purkinje
Purkinje cells in middle layer inhibit deep cerebellar nuclei (GABA)
dendritic tree flattened like an outstretched hand (looks like a bush in parasagittal
plane, twig in coronal plane)
each parasagittal band of Purkinje cells activated by specific coincidence of inputs
- cerebellar nuclei
spontaneously active, tonically excited all motor centres (brainstem and thalamic)
fastigial nucleus - posture and locomotion (brainstem)
interposed nuclei - reach and grasp (red nucleus and motor cortex)
dentate nucleus - fine skills (writing, speech, etc.)
- regulating the CPGs
a cluster of Purkinje cells activated at specific instant in motor performance
they inhibit a targe zone in the cerebellar nuclei
target sensorimotor area is disfacilitated, bringing some action to precise ending
- cerebellar dysfunction
motor elements drag on, can’t stop at precise phase in movement
ataxia - movements not balanced or coordinated
dysmetria - movements overshoot target
adiodokokinesis - can’t make fast transitions between opposing motions
- motor adaptation
when set of Purkinje cells is overactive, climbing fibre system discharges
direct powerful depolarization of Purkinje followed by inhibition
therefore increased vacilitation by cerebellar nuclei of targe sensorimotor areas
climbing fibres cause long-term depression of parallel fibre-Purkinje synapses
- inferior olive lesion
loss of abilit to adapt motor programs to new conditions
eg. throwing darts while wearing eye prism -> displacement error continues
indicates that parietal cortex can’t perform visuomotor recalibration w/o cerebellum
basal ganglia
- regulates flow of ‘volitional’ drive to premotor centres
- 2 tiers of nuclei
striatum - caudate, putatmen, nucleus accumbens
pallidum - globus pallidus (internal) and substantia nigra (pars reticulata)
- striatum (input tier)
excitatory input (glutamate) from cerebral cortex and centeromedian thalamus
topographic projection from cortex:
motor cortex -> putamen
prefrontal/parietal -> caudate
limbic cortex -> n. accumbens
thalamus conveys reticular formation input
- pallidum (output tier)
tonically inhibits (GABA) premotor centers
resting discharge rate of 70-90 imp/s
premotor centres activated by disinhibition
- forms a reiterative loop
cortex -> striatum -> pallidum -> thalamus -> premotor cortex -> cortex
- direct pathway (GO)
striatum inhibits pallidum
removes inhibition from thalamus, permits motor activity
- indirect pathway (STOP)
striatum inhibits GPe, which inhibits STN
STN excites pallidal output, which inhibits thalamus and prevents motor activity
- direct / indirect antagonism
focusing - paths act on different cells
adjusting speed or force - paths act on same cell
- striatal modulation
substantia nigra (SNc) dopaminergic neurons project to striatum
striatum chooses motor act, guided by cortical and reticular inputs
- dopamine and plasticity
dopaminergic neurons respond preferentially to reward-related stimuli
necessary for synaptic plasticity in striatum (motivational component)
- Parkinson’s disease
loss of dopaminergic neurons in substantia nigra and VTA ?
also loss of noradrenergic neurons in locus ceruleus
also loss of cholinergic neurons in pedunculopontine nucleus
symptoms: akinesia, bradykinesia, tremor, cogwheel rigidity, postural instability
too much STOP, not enough GO
- automatic routines
automatic chaining of motor elements into a habitual routine is lost in PD
each element in the sequence msut be individually commanded
replacing lost internal cues with external stimuli can help (eg. stripes on floor)
- Huntington’s disease
genetic disorder, chr 4, huntingtin >40 CAGs
loss of striatal neurons in indirect (STOP) pathway
unopposed GO pathway, excessive movement triggered in premotor centres
chronic involuntary movement of limbs, face and mouth (chorea)
- hemiballismus
discrete lesion in subthalamic nucleus
disinhibition of pallidum, spontaneous proximal limb movements
- dystonia
sustained muscle activity producing abnormal posture
focal, segmental or generalized
combination of dysfunction in basal ganglia and in cortex
focal can be use-dependent - eg. musicians and writeres
can sometimes stop with sensory stimulus - geste antagonistique
- pedunculopontine nucleus
glutamatergic neurons (mesencephalic locomotor centre) receive pallidal output
cholinergic neurons part of reticular activating system, up to 50% loss in PD
dysfunction in PPN may be responsible for rigidity in PD