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Motor System: Reflexes, Pyramidal
Tract and Basal Ganglia
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Overview of Motor Systems
Spinal and brainstem reflexes
Corticospinal and corticobulbar tracts
Cortical-subcortical-thalamo-corticalsystems
Involving basal ganglia
Involving pons and cerebellum
Involving nucleus accumbens
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Spinal and Brainstem Reflexes:Agonist and Antagonist Muscle
Groups
Sensory side
Muscle spindles Golgi tendon organs
Motor side
Alpha motor neurons: innervate skeletalmuscles, causing contraction
Gamma motor neurons: innervate musclespindles
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Golgi tendon organ
found in tendons near junctions with musclefibers: stretch receptors innervated by Ib
fibers: heavily myelinated with fastconduction; Ib fibers go to ventral horn andactivate interneurons which inhibit
(glycinergic) alpha motor neurons (oppositeof muscle spindle effect; negative feedback);higher threshold than for muscle spindle
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Muscle spindles
encapsulated structures within skeletalmuscle, containing intrafusal musclefibers, in parallel with extrafusal muscle
fibers (normal skeletal muscle); multiplenuclei in central region and intrafusalfibers at each end; two
morphological/functional types ofspindles
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Muscle spindles: Types
Nuclear bag fibers: clustered nuclei in center of spindle;dynamic: sensitive to rate of change in muscle length;static: sensitive to total change in muscle length;innervated by type Ia fibers: heavily myelinated, fastconduction: annulospiral nerve endings: firingfrequency proportional to degree of muscle stretch; alsoinnervated by dynamic or static gamma motor neurons:can contract the intrafusal fibers, stretching the centralregion, activating Ia afferents
Nuclear chain fibers: nuclei in row; sensitive to changein muscle length; innervated by type II fibers: flowerspray ending: codes event of stretch, not rate; gammamotor efferents
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Muscle spindle
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Innervation of muscle spindle and muscle
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Spinal cord circuits
1a afferents: activated by stretch ofmuscle; innervate alpha motor neurons,causing reflex contraction of muscle
1b afferents: activated by contraction ofmuscle; innervate interneurons, that inhibitalpha motor neurons, causing reflexrelaxation of muscle
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Stretch reflexes
1. passive stretch of muscle (e.g. bytapping tendon) activates Ia afferents,which activate alpha motor neurons, causingcontraction of stretched muscle:monosynaptic reflex
2. passive contraction of muscle
(stimulation of alpha motor neurons)causes decreased activity of musclespindles, leading to decreased activity ofalpha motor neurons
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Stretch reflexes
3. gamma loop: supraspinal input (e.g.corticospinal)activates gamma motor neurons,activating intrafusal fibers that stretch the musclespindle, activating Ia fibers, which activate alpha
motor neurons
4. voluntary muscle contraction against a load:
corticospinal fibers activate both alpha and gammamotor neurons, allowing Ia fibers to continue tosense muscle length while muscle is contracting:alpha-gamma coactivation
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Gammaefferentsallowcontinuedresponse ofspindleduringvoluntary
contraction
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Stretch reflexes
5. reciprocal or autogenic inhibition:activation of agonist and inhibition ofantagonist muscles; stretch of muscle
spindles activates Ia fibers, whichmonosynaptically activate agonist alphamotor neurons, and Ia fibers also activate
glycinergic interneurons which inhibitantagonist alpha motor neurons
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Stretch reflex
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Stretch reflexes
6. flexor reflex: activation of A-delta and cfibers by nociceptive stimuli activatesexcitatory and inhibitory interneurons in
ventral horn, which activate flexor alphamotor neurons and inhibit extensor motorneurons; involves several spinal cord
segments
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Flexor reflex
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Stretch reflexes
7. crossed extensor reflex: activation ofA-delta and c fibers by nociceptive stimuliactivates excitatory and inhibitory
interneurons in ventral horn, which projectacross midline to activate or inhibitinterneurons, resulting in activation of
extensor and inhibition of flexor motorneurons
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Crossedextensor
reflex
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Brainstem control over spinalreflexes
1. vestibulospinal tracts a. medial tract: originates in medial and inferior
vestibular nuclei; projects bilaterally to cervical andthoracic spinal cord; mostly controls neck muscles: reflex
control of head position: vestibular apparatus(semicircular canals, sacculus, utriculus) activatevestibular ganglion neurons that activate centralvestibular neurons
b. lateral tract: originates in lateral vestibular nucleus;projects ipsilaterally to entire spinal cord; innervatesalpha motor neurons (directly or indirectly) that controldeep back extensors and proximal limb extensors:maintain balance, antigravity muscles
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Brainstem control over spinalreflexes
2. reticulospinal tracts: innervate(indirectly) antigravity motor neurons;activated by cortico-reticular fibers and by
somatosensory inputs, especiallynociceptive
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Brainstem control over spinalreflexes
3. rubrospinal tract: crossed descendingsystems controlling mostly upper limbs;inputs from cerebral cortex and cerebellum
a. from magnocellular RN: rubrospinal tract;excites motor neurons controlling proximalflexors
b. from parvocellular RN: rubro-olivarytract
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Brainstem reflexes
A. blink reflexes
B. feeding mechanisms: rhythmic
chewing and licking movements
C. micturition (urination) reflex
D. gaze control
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Overview of Motor Systems
Spinal and brainstem reflexes
Corticospinal and corticobulbar tracts
Cortical-subcortical-thalamo-corticalsystems
Involving basal ganglia
Involving pons and cerebellum
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Corticospinal tract
Origins: primary motor cortex (MI),premotor cortex, supplemental motorcortex, anterior paracentral gyrus,parietal lobe (including SI) and cingulate
gyrus collaterals: small percentage of
corticospinal neurons
1. midbrain (primarily red nucleus) 2. trigeminal nuclei
3. pontine nuclei
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Corticospinal tract
Termination in spinal cord: mostlylaminae 3-7, few in ventral horn andlaminae 1-2; mostly innervating
interneurons, although some innervation ofalpha motor neurons
Neurotransmitter: glutamate and/oraspartate
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Pyramidaltract origin
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Corticobulbar tracts
A. control over facial muscles; bilateral input tomotor neurons controlling muscles in upper face, butcontralateral input to motor neurons controlling lower face(in humans, not sure about rodents)
B. control over muscles of mastication: motortrigeminal, and RF
C. control over external eye muscles: input comesfrom frontal and parietal eye fields, rather than from MI;projection to midbrain and paramedian pontine RF
D. control over tongue: hypoglossal and RF
E. control over swallowing reflexes: nucleusambiguus and RF
Control of movement by motor
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Control of movement by motorcortex
A. microstimulation studies: in MImovements of particular contralateral
joints (e.g. distal finger) can be elicited by
microstimulation; in MII contractions ofgroups of muscles sequentially to produceoverall movements of limbs, often
bilaterally
Control of movement by motor
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Control of movement by motorcortex
B. electrical activity during movement:corticospinal neurons active just before initiation ofa movement; activity related to amount of force
necessary to produce the movement; directionally-sensitive corticospinal neurons; higher-order motorcortex involved in calculating trajectories in space(probably in close communication with cerebellum)
and in planning larger-scale movements (probablyin close communication with the basal ganglia)
Control of movement by motor
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Control of movement by motorcortex
C. imaging studies in humans:random movements of digits activates MI(precentral gyrus); planned movements
activate MI and supplemental motorcortex; thinking about planned movementsactivates supplemental motor cortex, but
not MI
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Overview of Motor Systems
Spinal and brainstem reflexes
Corticospinal and corticobulbar tracts
Cortical-subcortical-thalamo-corticalsystems
Involving basal ganglia
Involving pons and cerebellum
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Cortex SubcorticalStructures
Thalamus
Cortical-Subcortical-Thalamo-Cortical Loops
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Motor Hierarchy and Loops
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Pallidum
Striatum
Motor
Thalamus: VA
Motor
Cortex
Basal Ganglia Loop
glutamate
GABAglu
GABA
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Basal Ganglia Structures
Striatum: dorsal striatum (caudate andputamen), ventral striatum (nucleusaccumbens and olfactory tubercle)
Pallidum: external and internal segmentsof globus pallidus
Subthalamic nucleus
Substantia nigra
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Striatum: extent
dorsal vs. ventral: dorsal = caudate andputamen; ventral = nucleus accumbens(Acb) and olfactory tubercle Tu; Tu
separated from striatum by ventralpallidum
core vs. shell of nucleus accumbens:core similar to caudate, shell transitionbetween striatum and extended amygdala
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Striatum: cell types
medium spiny: GABAergic projectionneurons that co-express neuropeptides:
enkephalinergic: PPE gene; D2 receptors
tachykininergic: extensive co-localization with
dynorphin: PPD/SP; D1 receptors other neuropeptides in much lower abundance
large cells: interneurons cholinergic: muscarinic receptors found on PPE
and PPD/SP neurons
NOS/NADPH d/somatostatin: GABAergic
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Medium spiny neuron
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Striatum: patch-matrixorganization
Mu receptors: demonstrate patches
Calbindin: most of matrix
Dendrites and axon collaterals ofprojection neurons mostly (but notalways) restricted to the compartmentof the parent neuron; dendrites and
axons of large neurons readily crosspatch-matrix boundaries
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Striatum: Afferent connections
cerebral cortex: come from layers 5 and 6: 5aand superficial 6 go to matrix, 5b and deep 6go to patch: may be related to development;glutamatergic
thalamus: input mostly from medialthalamus, including midline and intralaminarnuclei, many are collaterals of projections to
cortex, primarily Fr2 and Cg and insular substantia nigra: dopaminergic
Striatum: Dopaminergic
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Striatum: DopaminergicAfferents
From substantia nigra in midbrain
Nigra divided into pars compacta (SNc;contains most of dopaminergic cell bodies)and pars reticulata (SNr; contains dendrites
of dopaminergic neurons and GABAergiclocal neurons) Pars compacta divided into dorsal tier (co-
localized with calbindin; projects to patch
and part of cortex) and ventral tier (nocalbindin; projects to matrix)
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Striatum: Efferent connections
Globus pallidus: external and internalsegments; in rat, GP = GPe andentopeduncular n. = GPi
SNr: GABAergic neurons that inhibitdopaminergic neurons; alsoprojections to thalamus (VL, VM)
Cortico striatal pallidal
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Cortico-striatal-pallidal-thalamo-cortical loops
Direct path: cortex activates medium spiny neurons,which inhibit GPi neurons, decreasing the inhibitionof thalamo-cortical neurons; net effect is disinhibitionof the thalamus and facilitation of movement
Indirect path: cortex activates medium spinyneurons, which inhibit GPe neurons, which inhibitsubthalamic neurons, which tonically activate GPineurons, which inhibit thalamo-cortical neurons; neteffect is inhibition of thalamo-cortical neurons and
inhibition of movement
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Pallidum
Striatum
Motor
Thalamus: VA
Motor
Cortex
Basal Ganglia Loop
SubstantiaNigra
glutamate
GABAglu
DA
GABA
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Direct and Indirect Pathways Direct pathway
Disinhibits motorthalamus
Thus activatesthalamo-corticalneurons
Activates motorcortex
Facilitates movement
Indirect pathway
Inhibits motorthalamus
Thus inhibitsthalamo-corticalneurons
Inhibits motor cortex
Inhibits movement
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Direct and Indirect Pathways Direct pathway
Disinhibits motorthalamus
Thus activatesthalamo-corticalneurons
Activates motorcortex
Facilitates movement
Indirect pathway
Inhibits motorthalamus
Thus inhibitsthalamo-corticalneurons
Inhibits motor cortex
Inhibits movement
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Pallidum:Gpe, GPi
Striatum
Motor
Thalamus: VA
Motor
Cortex
Basal Ganglia Loop
SubstantiaNigra
glutamate
GABAglu
DA
Direct: +
Indirect: -
D1R, PPTD2R,
PPE
Subthalamic n.
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Dopaminergic control of striatum
Direct path:facilitatesmovement
Dopamine acts onD1 receptors, whichfacilitate informationflow
Dopamine facilitatesmovement
Indirect path:inhibits movement
Dopamine acts on
D2 receptors, whichinhibit informationflow, thusdisinhibition
Dopamine facilitatesmovement
Di t d I di t P th
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Direct and Indirect Pathways Direct: DA binds to D1
receptors activating adenylyl
cyclase, increasing cAMP,activating PKA
PKA phosphorylatesDARPP32
P-DARPP32 inhibits PP1phosphatase
unopposedphosphorylation ofvarious ion channels
Indirect: DA binds to D2receptors
inhibits AC, decreasescAMP, decreases activityof PKA
reduces phosphorylationof DARPP32
reduces inhibition of PP1 de-phosphorylates NR1
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Clinical problems in basal ganglia
Movement disorders are one aspect;cognitive and memory impairmentsmay also occur
Hypokinesias: akinesia (difficulty in planningand initiating movements); bradykinesia (reductionin velocity and amplitude of movement):inappropriate activity in antagonist muscles
Striatal strokes
Parkinsons disease
Dyskinesias (unwanted movements)
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Dopaminergic control of striatum
Direct path:facilitatesmovement
Dopamine acts onD1 receptors, whichfacilitate informationflow
Dopamine facilitatesmovement
Indirect path:inhibits movement
Dopamine acts on
D2 receptors, whichinhibit informationflow, thusdisinhibition
Dopamine facilitatesmovement
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Treatments for Parkinsons disease
Pharmacological L-DOPA plus carbidopa to increase dopamine
levels; usually initial improvements, but thenprogressive loss; D1 receptor agonists can inducetardive dyskinesia
Neurosurgical implantation of dopamine-producing cells: very
controversial
lesions of thalamic or pallidal structures: blocks
overactivity of pallido-thalamic projection overstimulation of subthalamus to inhibit
subthalamic activity: deep brain stimulation
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Clinical problems in basal ganglia
Huntingtons chorea Progressive, untreatable, decreased
function and dementia
Genetic defect in gene called huntingtin
Choreiform movements leading to severeimpairment; death within 15 years
Loss of about 90% of striatal neurons,especially of indirect pathway: overactivityof direct pathway: uncontrolled movements
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Functions of striatum
Much evidence for involvement instimulus-response learning, orprocedural memory: Packard and
Knowlton, Ann. Rev. Neurosci 25:563-593, 2002
Large-scale movements and
motivated behaviors (especially inventral striatum)