Motor System: Reflexes,
Pyramidal Tract and Basal
Ganglia
Richard Harlan, PhD
harlanre@tulane.edu
Overview of Motor Systems
• Spinal and brainstem reflexes
• Corticospinal and corticobulbar
tracts
• Cortical-subcortical-thalamo-cortical
systems
– Involving basal ganglia
– Involving pons and cerebellum
– Involving nucleus accumbens
Spinal and Brainstem Reflexes:
Agonist and Antagonist Muscle
Groups
• Sensory side
– Muscle spindles
– Golgi tendon organs
• Motor side
– Alpha motor neurons: innervate skeletal
muscles, causing contraction
– Gamma motor neurons: innervate
muscle spindles
Golgi tendon organ
• found in tendons near junctions with
muscle fibers: stretch receptors
innervated by Ib fibers: heavily
myelinated with fast conduction; Ib fibers
go to ventral horn and activate
interneurons which inhibit (glycinergic)
alpha motor neurons (opposite of muscle
spindle effect; negative feedback); higher
threshold than for muscle spindle
Muscle spindles
• encapsulated structures within
skeletal muscle, containing intrafusal
muscle fibers, in parallel with
extrafusal muscle fibers (normal
skeletal muscle); multiple nuclei in
central region and intrafusal fibers at
each end; two
morphological/functional types of
spindles
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, fast
conduction: annulospiral nerve endings: firing
frequency proportional to degree of muscle stretch; also
innervated by dynamic or static gamma motor neurons:
can contract the intrafusal fibers, stretching the central
region, activating Ia afferents
• Nuclear chain fibers: nuclei in row; sensitive to change
in muscle length; innervated by type II fibers: flower
spray ending: codes event of stretch, not rate; gamma
motor efferents
Muscle spindle
Innervation of muscle spindle and muscle
Spinal cord circuits
• 1a afferents: activated by stretch of
muscle; innervate alpha motor
neurons, causing reflex contraction
of muscle
• 1b afferents: activated by contraction
of muscle; innervate interneurons,
that inhibit alpha motor neurons,
causing reflex relaxation of muscle
Stretch reflexes
• 1. passive stretch of muscle (e.g. by
tapping tendon) activates Ia afferents,
which activate alpha motor neurons,
causing contraction of stretched muscle:
monosynaptic reflex
• 2. passive contraction of muscle
(stimulation of alpha motor neurons)
causes decreased activity of muscle
spindles, leading to decreased activity of
alpha motor neurons
Stretch reflex
Stretch reflexes
• 3. gamma loop: supraspinal input (e.g.
corticospinal) activates gamma motor neurons,
activating intrafusal fibers that stretch the
muscle spindle, activating Ia fibers, which
activate alpha motor neurons
• 4. voluntary muscle contraction against a load:
corticospinal fibers activate both alpha and
gamma motor neurons, allowing Ia fibers to
continue to sense muscle length while muscle is
contracting: alpha-gamma coactivation
Gamma
efferents
allow
continued
response of
spindle
during
voluntary
contraction
Stretch reflexes
• 5. reciprocal or autogenic inhibition:
activation of agonist and inhibition of
antagonist muscles; stretch of
muscle spindles activates Ia fibers,
which monosynaptically activate
agonist alpha motor neurons, and Ia
fibers also activate glycinergic
interneurons which inhibit antagonist
alpha motor neurons
Stretch reflex
Stretch reflexes
• 6. flexor reflex: activation of A-delta
and c fibers by nociceptive stimuli
activates excitatory and inhibitory
interneurons in ventral horn, which
activate flexor alpha motor neurons
and inhibit extensor motor neurons;
involves several spinal cord
segments
Flexor reflex
Stretch reflexes
• 7. crossed extensor reflex: activation
of A-delta and c fibers by nociceptive
stimuli activates excitatory and
inhibitory interneurons in ventral
horn, which project across midline to
activate or inhibit interneurons,
resulting in activation of extensor
and inhibition of flexor motor
neurons
Crossed
extensor
reflex
Brainstem control over
spinal reflexes
• 1. vestibulospinal tracts
– a. medial tract: originates in medial and inferior
vestibular nuclei; projects bilaterally to cervical and
thoracic spinal cord; mostly controls neck muscles:
reflex control of head position: vestibular apparatus
(semicircular canals, sacculus, utriculus) activate
vestibular ganglion neurons that activate central
vestibular neurons
– b. lateral tract: originates in lateral vestibular
nucleus; projects ipsilaterally to entire spinal cord;
innervates alpha motor neurons (directly or
indirectly) that control deep back extensors and
proximal limb extensors: maintain balance,
antigravity muscles
Brainstem control over
spinal reflexes
• 2. reticulospinal tracts: innervate
(indirectly) antigravity motor
neurons; activated by corticoreticular fibers and by
somatosensory inputs, especially
nociceptive
Brainstem control over
spinal reflexes
• 3. rubrospinal tract: crossed
descending systems controlling
mostly upper limbs; inputs from
cerebral cortex and cerebellum
– a. from magnocellular RN: rubrospinal
tract; excites motor neurons controlling
proximal flexors
– b. from parvocellular RN: rubro-olivary
tract
Brainstem reflexes
•
•
A. blink reflexes
B. feeding mechanisms: rhythmic
chewing and licking movements
•
C. micturition (urination) reflex
•
D. gaze control
Overview of Motor Systems
• Spinal and brainstem reflexes
• Corticospinal and corticobulbar
tracts
• Cortical-subcortical-thalamo-cortical
systems
– Involving basal ganglia
– Involving pons and cerebellum
Corticospinal tract
• Origins: primary motor cortex (MI),
premotor cortex, supplemental motor
cortex, 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
Corticospinal tract
• Termination in spinal cord: mostly
laminae 3-7, few in ventral horn and
laminae 1-2; mostly innervating
interneurons, although some
innervation of alpha motor neurons
• Neurotransmitter: glutamate and/or
aspartate
Pyramidal
tract origin
Corticobulbar tracts
•
•
•
•
•
A. control over facial muscles; bilateral input to
motor neurons controlling muscles in upper face, but
contralateral input to motor neurons controlling
lower face (in humans, not sure about rodents)
B. control over muscles of mastication: motor
trigeminal, and RF
C. control over external eye muscles: input
comes from 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: nucleus
ambiguus and RF
Control of movement by
motor cortex
•
A. microstimulation studies: in MI
movements of particular
contralateral joints (e.g. distal finger)
can be elicited by microstimulation;
in MII contractions of groups of
muscles sequentially to produce
overall movements of limbs, often
bilaterally
Control of movement by
motor cortex
•
B. electrical activity during movement:
corticospinal neurons active just before
initiation of a movement; activity related to
amount of force necessary to produce the
movement; directionally-sensitive corticospinal
neurons; higher-order motor cortex involved in
calculating trajectories in space (probably in
close communication with cerebellum) and in
planning larger-scale movements (probably in
close communication with the basal ganglia)
Control of movement by
motor cortex
•
C imaging studies in humans:
random movements of digits
activates MI (precentral gyrus);
planned movements activate MI and
supplemental motor cortex; thinking
about planned movements activates
supplemental motor cortex, but not
MI
Overview of Motor Systems
• Spinal and brainstem reflexes
• Corticospinal and corticobulbar
tracts
• Cortical-subcortical-thalamo-cortical
systems
– Involving basal ganglia
– Involving pons and cerebellum
Cortical-Subcortical-Thalamo-Cortical Loops
Cortex
Subcortical
Structures
Thalamus
Motor Hierarchy and Loops
Basal Ganglia Loop
Motor
Cortex
glutamate
Striatum
GABA
glu
Motor
Thalamus: VA
GABA
Pallidum
Basal Ganglia Structures
• Striatum: dorsal striatum (caudate
and putamen), ventral striatum
(nucleus accumbens and olfactory
tubercle)
• Pallidum: external and internal
segments of globus pallidus
• Subthalamic nucleus
• Substantia nigra
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Striatum: extent
• dorsal vs. ventral: dorsal = caudate
and putamen; ventral = nucleus
accumbens (Acb) and olfactory
tubercle Tu; Tu separated from
striatum by ventral pallidum
• core vs. shell of nucleus accumbens:
core similar to caudate, shell
transition between striatum and
extended amygdala
Striatum: cell types
• medium spiny: GABAergic projection
neurons 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
Medium spiny neuron
Striatum: patch-matrix
organization
• Mu receptors: demonstrate patches
• Calbindin: most of matrix
• Dendrites and axon collaterals of
projection neurons mostly (but not
always) restricted to the
compartment of the parent neuron;
dendrites and axons of large neurons
readily cross patch-matrix
boundaries
Striatum: Afferent
connections
• cerebral cortex: come from layers 5 and 6:
5a and superficial 6 go to matrix, 5b and
deep 6 go to patch: may be related to
development; glutamatergic
• thalamus: input mostly from medial
thalamus, including midline and
intralaminar nuclei, many are collaterals of
projections to cortex, primarily Fr2 and Cg
and insular
• substantia nigra: dopaminergic
Striatum: Dopaminergic
Afferents
• 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
GABAergic local neurons)
• Pars compacta divided into dorsal tier (colocalized with calbindin; projects to patch
and part of cortex) and ventral tier (no
calbindin; projects to matrix)
Striatum: Efferent
connections
• Globus pallidus: external and
internal segments; in rat, GP = GPe
and entopeduncular n. = GPi
• SNr: GABAergic neurons that inhibit
dopaminergic neurons; also
projections to thalamus (VL, VM)
Cortico-striatal-pallidalthalamo-cortical loops
• Direct path: cortex activates medium spiny
neurons, which inhibit GPi neurons, decreasing
the inhibition of thalamo-cortical neurons; net
effect is disinhibition of the thalamus and
facilitation of movement
• Indirect path: cortex activates medium spiny
neurons, which inhibit GPe neurons, which inhibit
subthalamic neurons, which tonically activate
GPi neurons, which inhibit thalamo-cortical
neurons; net effect is inhibition of thalamocortical neurons and inhibition of movement
Basal Ganglia Loop
Motor
Cortex
glu
Motor
Thalamus: VA
glutamate
Striatum
Substantia
Nigra
DA
GABA
GABA
Pallidum
Direct and Indirect Pathways
• Direct pathway
– Disinhibits motor
thalamus
– Thus activates
thalamo-cortical
neurons
– Activates motor
cortex
– Facilitates
movement
• Indirect pathway
– Inhibits motor
thalamus
– Thus inhibits
thalamo-cortical
neurons
– Inhibits motor
cortex
– Inhibits movement
Direct and Indirect Pathways
• Direct pathway
– Disinhibits motor
thalamus
– Thus activates
thalamo-cortical
neurons
– Activates motor
cortex
– Facilitates
movement
• Indirect pathway
– Inhibits motor
thalamus
– Thus inhibits
thalamo-cortical
neurons
– Inhibits motor
cortex
– Inhibits movement
Basal Ganglia Loop
Motor
Cortex
glu
glutamate
Striatum
Substantia
Nigra
DA
D2R,
PPE
Motor
Thalamus: VA
GABA
D1R, PPT
Direct: +
Indirect: -
Pallidum:
Gpe, GPi
Subthalamic n.
Dopaminergic control of
striatum
• Direct path:
facilitates
movement
• Dopamine acts on
D1 receptors,
which facilitate
information flow
• Dopamine
facilitates
movement
• Indirect path:
inhibits movement
• Dopamine acts on
D2 receptors,
which inhibit
information flow,
thus disinhibition
• Dopamine
facilitates
movement
Direct and Indirect Pathways
• Direct: DA binds to D1
receptors
• activating adenylyl
cyclase, increasing
cAMP, activating PKA
• PKA phosphorylates
DARPP32
• P-DARPP32 inhibits
PP1 phosphatase
• unopposed
phosphorylation of
various ion channels
• Indirect: DA binds to
D2 receptors
• inhibits AC, decreases
cAMP, decreases
activity of PKA
• reduces
phosphorylation of
DARPP32
• reduces inhibition of
PP1
• de-phosphorylates
NR1
Clinical problems in basal ganglia
• Movement disorders are one aspect;
cognitive and memory impairments
may also occur
• Hypokinesias: akinesia (difficulty in planning
and initiating movements); bradykinesia (reduction
in velocity and amplitude of movement):
inappropriate activity in antagonist muscles
– Striatal strokes
– Parkinson’s disease
• Dyskinesias (unwanted movements)
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Dopaminergic control of
striatum
• Direct path:
facilitates
movement
• Dopamine acts on
D1 receptors,
which facilitate
information flow
• Dopamine
facilitates
movement
• Indirect path:
inhibits movement
• Dopamine acts on
D2 receptors,
which inhibit
information flow,
thus disinhibition
• Dopamine
facilitates
movement
Treatments for Parkinson’s disease
• Pharmacological
– L-DOPA plus carbidopa to increase dopamine
levels; usually initial improvements, but then
progressive loss; D1 receptor agonists can
induce tardive 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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Dyskinesias and hyperkinesias
• choreiform movements: “dance-like movements”
e.g. Huntington's disease
• ballisms and hemiballisms; usually vascular
lesions of contralateral subthalamic nucleus
• athetoid movements: continual writhing
movements of distal extremity
• myoclonus: sudden jerky movements
• dystonia: chronic muscular contractions leading
to bending or twisting
• tardive dyskinesia: iatrogenic (caused by
medications)
Clinical problems in basal
ganglia
• Huntington’s chorea
– Progressive, untreatable, decreased
function and dementia
– Genetic defect in gene called huntingtin
– Choreiform movements leading to severe
impairment; death within 15 years
– Loss of about 90% of striatal neurons,
especially of indirect pathway: overactivity
of direct pathway: uncontrolled movements
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Normal
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Huntington’s Chorea
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Functions of striatum
• Much evidence for involvement in
stimulus-response learning, or
procedural memory: Packard and
Knowlton, Ann. Rev. Neurosci 25:
563-593, 2002
• Large-scale movements and
motivated behaviors (especially in
ventral striatum)