Prelims IX - Motor II - Motor Tracts

7/25/2019 Prelims IX - Motor II - Motor Tracts

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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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2. reticulospinal tracts: innervate(indirectly) antigravity motor neurons;activated by cortico-reticular fibers and by

somatosensory inputs, especiallynociceptive


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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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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



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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)



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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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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


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


Indirect path:inhibits movement

Dopamine acts on

D2 receptors, whichinhibit informationflow, thusdisinhibition



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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)

Prelims IX - Motor II - Motor Tracts

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