motor system and basal ganglia

framework A

equilibrium
gross movements of the limbs
fine, distal, voluntary movements

framework B

reflexive - local sign
rhythmic - walking, chewing, can be thought of as more complex reflex
volitional - goal directed

normal motor control

LMN, spinal region connections, UMN, control circuits that modulate activity in the descending pathways, motor planning areas
disturbance of any can lead to abnormal mvmt

alpha motor neurons

cell bodies in the ventral horn and CN motor nuclei, innervate extrafusal (skeletal) muscle
large, myelinated axons

gamma motor neurons

cell bodies in ventral horn and trigeminal motor nucleus, innervates intrafusal fibers in the muscle spindle
medium, myelinated axons
do not cause mvmt, important for motor control

motor unit

alpha MN and all muscle fibers innervated by it, NMJ designed so that every time AP comes down muscle twitches (always excitatory)
neuron innervating muscle determines type

muscle fiber deinnervation

allows muscle fiber type to change if reinnervated by different type of neuron
under normal circumstances motor unit fibers distributed throughout muscle but with reinnervation may be collected in one spot which changes the biomechanical pull

slow twitch muscle fiber

small diameter, mainly postural muscles
aerobic, maintain static low level tension

fast fatigable muscle fiber

large diameter
anaerobic, high tension not sustainable

motor unit recruitment

Henneman’s size principle: slow twitch activated first

number of fibers in motor unit

power muscles have higher ratio, precise muscles have lower ratio for good motor control

LMN activity depends on convergence of

peripheral sensory info, spinal circuitry, descending pathways
combination determines how vigorously fires off

peripheral sensory info from

golgi tendon organ, muscle spindles, cutaneous receptors

golgi tendon organ

muscle tension info relayed to alpha MN via interneurons

muscle spindle

muscle length and velocity of change info
LMN reflexively corrects small errors, sensitivity adjusted by gamma MN

cutaneous receptors

DT, pain, temp

spinal circuitry

reflexes
involuntary response to external stimuli, can operate without supraspinal input but normally influenced by changing background levels
response is context dependent, not locked into single movement pattern

DTR

aka muscle stretch reflex, phasic stretch reflex
quick stretch → Ia afferents stimulated → alpha MN → contract muscle
monosynaptic reflex, sensory and effector limb are same nerve

reciprocal inhibition

inhibit antagonist muscle, same mechanism as DTR plus an inhibitory nerve
quick stretch → Ia afferents stimulated → inhibitory interneuron → antagonist alpha MN inhibited

tonic stretch reflex

multisynaptic, see with people with UMN problems
primary and secondary spindle endings → excitatory interneurons → alpha MN of same muscle
facilitatory effect, builds over time

golgi tendon organ reflex

autogenic inhibition
tendon tension Ib afferents → inhibitory interneurons → alpha MN of same muscle
modulatory effect on force control

proprioceptive reflexes

DTR, reciprocal inhibition, tonic stretch reflex, golgi tendon organ reflex

withdrawal reflex

cutaneous reflex, specific motor pattern associated with location of noxious stimulant
multisynaptic, context dependent, multiple muscles involved
connections across multiple cord segments to activate necessary muscles to move away from stimulus

muscle synergies

muscles that are often activated together, can be normal or pathological if it dominates movement

central pattern generators

groups of neurons that form a flexible circuit coordinating purposeful movement automatically
rhythmic/complex mvmt, rhythmic such as stepping

locomotion generator

pattern not dependent on afferent but afferent input more important in adjusting pattern
stepping reflex in infants can return with change in weight, seen with anencephaly

descending pathways

tracts, whichever one is dominant determines response

basal ganglia

motor control circuit, no direct connections to LMN so act through intermediaries
primarily exerts influence through motor planning areas or pedunculopontine nuclei

basal ganglia functions

sequencing movement, regulate muscle tone and force, habit formation and motor learning
cognitive: awareness body orientation, motivation, ability to change behavior

pedunculopontine nuclei

reticular formation nucleus in caudal midbrain
afferents: globus pallidus and substantia nigra reticularis
efferents: vestibular nuclei, reticular areas going to reticulospinal tract, inf part of frontal cortex
stimulation elicits rhythmical movements

globus pallidus internus

primary output nucleus, whatever happens to globus pallidus internus happens to substantia nigra reticularis

basal ganglia functional loop

all loops use direct and indirect pathways
motor loop: somatomotor control
oculomotor loop: control of orientation and gaze
dorsolateral prefrontal and orbitofrontal loop: cognitive function
limbic loop: emotional and visceral function

NTs in the basal ganglia

glutamate excitatory, GABA inhibitory, dopamine excitatory or inhibitory depending on receptor

disinhibition

mechanism that releases cell from inhibition, tonically active - holds target cell in check
excitatory neuron followed by 2 inhibitory neurons followed by target neuron

direct (go) pathway

thalamus disinhibition, facilitates thalamocortical projections, associated with more movement
cerebral cortex → excitatory corticostriatal fibers → putamen → inhibitory striatopallidal fibers → globus pallidus internus → tonically inhibitory pallidothalamic → less inhibition of motor thalamus to release movement → increased excitation thalamocortical projections

indirect (no go) pathway

subthalamus disinhibition, inhibits thalamocortical projections, decreased movement
cerebral cortex → excitatory corticostriatal fibers → putamen → inhibitory striatopallidal fibers → globus pallidus externus → tonically inhibitory pallidosubthalamic fibers → subthalamus → excitatory subthalamicpallidal fibers → globus pallidus internus → inhibitory pallidothalamic fibers → inhibit motor thalamus to prevent unwanted movements

stop pathway

stops ongoing movement
cerebral cortex → excite subthalamus → excite globus pallidus internus → inhibit motor thalamus and stop ongoing movement

substantia nigra

affects direct and indirect pathways, melanin containing cells produce dopamine
D1 receptor: facilitates activity in direct pathway, excitatory
D2 receptor: inhibits activity in indirect pathway
decreased dopamine always leads to less movement

dopamine and direct pathway

excitation from both dopamine and motor cortex leads to more movement
degeneration decreases activation of 1st inhibitory neuron leading to decreased inhibition of 2nd so more inhibition of thalamus → less movement

dopamine and indirect pathway

inhibition from dopamine and excitation from motor cortex
degeneration decreases inhibition which turns up indirect pathway leading to less movement

disturbances of basal ganglia

imbalance between thalamic and subthalamic disinhibition mechanisms

akinesia

impaired ability to initiate movement, disruption of motor planning
hypokinetic disorder

bradykinesia

decreased movement velocity and amplitude, imbalance of direct and indirect pathways
loss of inhibitory connection between striatum and globus pallidus internus
hypokinetic disorder

Parkinson’s disease

3rd most common neuro disorder, progressive, usually over 55
decreased dopamine leads to decreased movement via both direct and indirect pathways, less activation volitional muscles via corticospinal tract
axial rigidity from increased inhibition of GPi on pedunculopontine nucleus which disinhibits the reticulospinal tracts leading to rigidity

PD movement disorders

tremor at rest, cogwheel rigidity, akinesia, bradykinesia, eye mvmt disturbances, loss of postural reflexes

PD etiology

loss of melanin containing dopaminergic neurons in substantia nigra

PD treatment

L-dopa or L-dopa and carbidopa: L-dopa converts to dopamine, carbidopa reduces peripheral uptake, efficacy declines with long term use
MOA inhibitors: slow progression of disease
embryological tissue implants: stem cells to produce dopamine injected in lat ventricles
surgical: pallidotomy
deep brain stimulation: in globus pallidus or subthalamus, precise, can excite or inhibit tissue

hyperkinetic disorders

disruption of indirect pathway, lose inhibition of thalamic motor nucleus

ballism

uncontrolled flinging movements of UE or LE, hyperkinetic disorder
vascular lesions of contra subthalamic nucleus cause hemiballism

choreiform

generalized irregular dance like movements of limbs, hyperkinetic disorder

Huntington’s disease

progressive untreatable disorder, death 10-15 yrs post onset, genetic disorder
also affects caudate which has effects on cognition and behavior
degenerates striatum leading to hyperkinesia early but can have more global affects with progression

early stage huntington’s

irritability, absent-minded, depression, clumsiness, falls

mid stage huntington’s

choreiform movements, cognitive function decreases, speech deteriorates

late stage huntington’s

dementia

huntington’s disease neuroscience

hyperkinesia: decreased inhibition of motor thalamus leads to increased corticospinal activity
axial muscles: decreased inhibition of pedunculopontine leads to increased inhibition of reticulospinal tracts → decreased axial tone

Huntington’s etiology

selective loss of spiny cells in striatum projecting to lateral pallidum which is 1st inhibitory in indirect pathway
selective loss of Ach cells in striatal complex

other hyperkinetic disorders

CP athetoid mvmt: continuous writhing of distal portions of extremity
tourette’s syndrome: vocal or motor tics
dystonia: involuntary sustained motor contractions

tardive dyskinesia

medically induced disorder secondary to chronic treatment antipsychotics and neuroleptic drugs: blocking dopamine leads brain to increase sensitivity to it causing an imbalance in dopamine pathway
involuntary movement particularly of face and tongue