Cerebellum

Beside from the areas in the cerebral cortex that stimulate muscle contraction, two other brain
structuresare also essential for normal motor function. They are the cerebellum and the basal ganglia.
Yet neither of these two can control muscle function by themselves. Instead, they always function in
association with other systems of motor control. Basically, the cerebellum plays major roles in the
timing of motor activities and in rapid, smooth progression from one muscle movement to the next. It
also helps to control intensity of muscle contraction when the muscle load changes, as well as
controlling necessary instantaneous interplay between agonist and antagonist muscle groups.

The cerebellum is situated in the posterior cranial fossa and is covered superiorly by the tentorium
cerebelli. It is the largest part of the hindbrain and lies posterior to the fourth ventricle, It is connected
to the posterior aspect of segment of the brain stem by its cerebellar peduncles, connected to medulla
oblongata by inferior cerebellar peduncle (restiform
restiform body) ,connected to pons by middle cerebellar
peduncle( brachium pontis) and connected to mid brain by superior cerebellar peduncle( brachium
conjunctivum).
conjunctivum) Cerebellum consists of two cerebellar hemispheres joined by a narrow median vermis.

Functions of the cerebellum

1.Maintenance of balance and posture. The cerebellum is important for making postural adjustments in
order to maintain balance. Through its input from vestibular receptors and proprioceptors, it
modulates commands to motor neurons to compensate for shifts in body position or changes in load
upon muscles. Patients with cerebellar damage suffer from balance disorders, and they often develop
stereotyped postural strategies to compensate for this problem (e.g., a wide-based gait).

2.Coordination of voluntary movements. Most movements are composed of a number of different

muscle groups acting together in a temporally coordinated fashion. One major function of the
cerebellum is to coordinate the timing and force of these different muscle groups to produce fluid limb
or body movements.

3.Motor learning. The cerebellum is important for motor learning. The cerebellum plays a major role
in adapting and fine-tuning motor programs to make accurate movements through a trial-and-error
process (e.g., playing a piano).

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Divisions of the cerebellum.
cerebellum.
Anatomically Cerebellum is divided horizontally in to three major divisions flocculonodular lobe,
lobe,
posterior lobe and an anterior lobe . The cerebellum is also divided sagittally ( longitudinally) into
three zones that run from medial to lateral. The vermis is located along the midsagittal plane of the
cerebellum. Directly lateral to the vermis is the intermediate zone.
zone Finally, the lateral hemispheres are
located lateral to the intermediate zone.
Longitudinal Functional Divisions
Divisions of the Anterior and Posterior
Lobes.
Note down the center of the cerebellum a narrow band called the vermis, separated from the remainder
of the cerebellum by shallow grooves. In this area, most cerebellar control functions for muscle
movements of the axial body, neck, shoulders, and hips are located. To each side of the vermis is a
large, laterally protruding cerebellar hemisphere, and each of these hemispheres
is divided into an intermediate zone and a lateral zone. The intermediate zone of the hemisphere is
concerned with controlling muscle contractions in the distal portions of the upper and lower limbs,
especially the hands and fingers and feet and toes. The lateral zone of the hemisphere operates at a
much more remote level because this area joins with the cerebral cortex in the overall planning of
sequential motor movements. Without this lateral zone, most discrete motor activities of the body lose
their appropriate timing and sequencing and therefore become in coordination.,

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Functional division of cerebellum.
Vestibulocerebellum.
Vestibulocerebellum

The vestibulocerebellum comprises the flocculonodular lobe and its connections with the lateral
vestibular
vestibular nuclei.
nuclei Phylogenetically, the vestibulocerebellum is the oldest part of the cerebellum. As its
name implies, it is involved in vestibular reflexes and in postural maintenance.

Spinocerebellum.

The spinocerebellum comprises the vermis and the intermediate zones of the cerebellar cortex, as well
as the fastigial and interposed nuclei.
nuclei As its name implies, it receives major inputs from the
spinocerebellar tract. Its output projects to rubrospinal, vestibulospinal, and reticulospinal tracts. It is
involved in the integration of sensory input with motor commands to produce adaptive motor
coordination. Phylogenetically it is the Paleocerebllum.

Cerebrocerebellum.

The cerebrocerebellum is the largest functional subdivision of the cerebellum, comprising the lateral
hemispheres and the dentate nuclei.
nuclei Its name derives from its extensive connections with the cerebral
cortex, via the pontine nuclei (afferents) and the VA and VL thalamus (efferent's). It is involved in the
planning and timing of movements. Phylogenetically it is the neocerebellum

Structure of the Cerebellum

The cerebellum is composed of an outer covering of gray matter called the cortex and inner white
matter. Embedded in the white matter of each hemisphere are three masses of gray matter forming the
deepcerebellar nuclei.

Deep Cerebellar nuclei.

All outputs from the cerebellum originate from the Deep cerebellar nuclei.
nuclei. Thus, a lesion to the
cerebellar nuclei has the same effect as a complete lesion of the entire cerebellum.

1. The fastigial nucleus(Roof

nucleus(Roof Nucleus) is the most medially located of the cerebellar nuclei. It
receives input from the vermis and from cerebellar afferents that carry vestibular, proximal

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 somatosensory, auditory, and visual information. It projects to the vestibular nuclei and the
reticular formation.
2. The interposed nuclei (globose and emboliform nucleus). They are situated lateral to the
fastigial nucleus. They receive input from the intermediate zone and from cerebellar afferents
that carry spinal, proximal somatosensory, auditory, and visual information. They project to
the contralateral red nucleus.
nucleus
3. The dentate nucleus is the largest of the cerebellar nuclei, located lateral to the interposed
nuclei. It receives input from the lateral hemisphere and from cerebellar afferents that carry
information from the cerebral cortex (via the pontine nuclei). It projects to the contralateral red
nucleus and the ventrolat
ventrolateral (VA&
(VA&VL)
VA&VL) thalamic nucleus.
nucleus

Structure of the Cerebellar Cortex

The gray matter of the cerebellar cortex is divided into three layers: (1) an outer molecular layer(2) a
middle layer, the Purkinje cell layer; and (3) an internal layer granular layer.

The molecular layer,

layer is made of the stellate, basket cells and axons of granule cells and the dendrites of
Purkinje cells

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The Purkinje layer. The Purkinje cells are large Golgi type I neurons. They are flask shaped and are
arranged in a single layer. There are about 50.0000000.00 Purkinje cells present . Purkinje cells are
some of the largest neurons in the human brain, the dendrites of purkinje cells are seen to pass into
the molecular layer, where they undergo profuse branching. The primary and secondary branches are
smooth, and subsequent branches are covered by short, thick dendritic spines. It has been shown that
the spines form synaptic contacts with the parallel fibers derived from the granule cell axons. Axons of
the Purkinje cells arising from the base of the purkinje cells send inhibitory projections to the deep
cerebellar nuclei, and they are the only output of the cerebellar cortex. A few of the Purkinje cell axons
pass directly to end in the vestibular nuclei of the brainstem.

The granular layer is packed with small cells with densely staining nuclei and scanty cytoplasm
clawlike endings and have synaptic contact with mossy fiber input . The axon of each granule cell
passes into the molecular layer, where it bifurcates at a T junction, the branches running parallel to the
long axis of the cerebellar folium . These fibers, known as parallel fibers, run at right angles to the
dendritic processes of the Purkinje cells. Most of the parallel fibers make synaptic contacts with the
spinous processes of the dendrites of the Purkinje cells. Another type of cells present in granular layer
are Golgi cells . Their dendrites ramify in the molecular layer, and their axons terminate by splitting
up into branches that synapse with the dendrites of the granular cells

Functional Unit of the Cerebellar Cortex

CortexThe Purkinje Cell and the Deep Nuclear Cell
The cerebellum has about 30 million nearly identical functional units, one of which is shown in
the Picture This functional unit centers on a single, very large Purkinje cell (30 million of which are in
the cerebellar cortex) and on a corresponding deep nuclear cell.

Neuronal Circuit of the Functional Unit shown in the picture is the neuronal circuit of the functional
unit, which is repeated with little variation 30 million times in the cerebellum. The output from the
functional unit is from a deep nuclear cell. This cell is continually under both excitatory and inhibitory
influences. The excitatory influences arise from direct connections with afferent fibers that enter the
cerebellum from the brain or the periphery. The inhibitory
influence arises entirely from the Purkinje cell in the cortex of the cerebellum. The afferent inputs to
the cerebellum are mainly of two types, one called the climbing fiber type and the other called the
mossy fiber type. The climbing fibers all originate from the inferior olives of the medulla. There is one
climbing fiber for about 5 to 10 Purkinje cells. After sending branches to several deep nuclear cells, the
climbing fiber continues all the way to the outer layers of the cerebellar cortex, where it makes about
300 synapses with the soma

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and dendrites of each Purkinje cell. This climbing fiber is distinguished by the fact that a single
impulse in it will always cause a single, prolonged (up to 1 second), peculiar type of action potential in
each Purkinje cell with which it connects, beginning with a strong spike and followed by a trail of
weakening secondary spikes. This action potential is called the complex spike.

The mossy fibers are all the other fibers that enter the cerebellum from multiple sources: from the
higher brain, brain stem, and spinal cord. These fibers also send collaterals to excite the deep nuclear
cells. Then they proceed to the granule cell layer of the cortex, where they too synapse with hundreds
to thousands of granule cells. In turn, the granule cells send very, very small axons, less than 1
micrometer in diameter, up to
the molecular layer on the outer surface of the cerebellar cortex. Here the axons divide into two
branches that extend 1 to 2 millimeters in each direction parallel to the folia. There are many millions
of these parallel nerve fibers because there are some 500 to 1000 granule cells for every 1 Purkinje cell.
It is into this molecular layer that the dendrites of the Purkinje cells project and 80,000 to 200,000 of
the parallel fibers synapse with each Purkinje cell. The mossy fiber input to the Purkinje cell is quite
different from the climbing fiber input because their synaptic connections are weak, so that large
numbers of mossy fibers must be stimulated simultaneously to excite the Purkinje cell. Furthermore,
activation usually takes the form of a much weaker short duration Purkinje cell action potential called
a simple spike, rather than the prolonged complex action potential caused by climbing fiber input.

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Afferents Of Cerebellum

Pathway Function Origin Destination

Corticopontocerebellar Conveys control from Frontal, parietal, Via pontine nuclei and
cerebral cortex temporal, and mossy fibers to cerebellar
occipital lobes cortex
Cerebro-olivocerebellar Conveys control from Frontal, parietal, Via inferior olivary nuclei
cerebral cortex temporal, and and climbing fibers to
occipital lobes cerebellar cortex
Cerebroreticulocerebellar Conveys control from Sensorimotor Via reticular formation
cerebral cortex areas
Anterior spinocerebellar Conveys information from Muscle spindles, Via mossy fibers to
muscles and joints tendon organs, cerebellar cortex
and joint
receptors

Posterior spinocerebellar Conveys information from Muscle spindles, Via mossy fibers to
muscles and joints tendon organs, cerebellar cortex
and joint
receptors
Cuneocerebellar Conveys information from Muscle spindles, Via mossy fibers to
muscles and joints of tendon organs, cerebellar cortex
upper limb and joint
receptors

Vestibular nerve Conveys information of Utricle, saccule, Via mossy fibers to cortex of
head position and and semicircular flocculonodular lobe
movement canals

Other afferents Conveys information from Red nucleus, Cerebellar cortex

midbrain tectum

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Efferent's Of the Cerebellum
Pathway Function Origin Destination
Globose- Influences Globose and To contralateral red nucleus, then
emboliform- ipsilateral emboliform nuclei via crossed rubrospinal tract to
rubral motor activity ipsilateral motor neurons in spinal
cord

Dentothalamic Influences Dentate nucleus To contralateral ventrolateral

ipsilateral nucleus of thalamus, then to
motor activity contralateral motor cerebral
cortex; corticospinal tract crosses
midline and controls ipsilateral
motor neurons in spinal cord

Fastigial Influences Fastigial nucleus Mainly to ipsilateral and to

vestibular ipsilateral contralateral lateral vestibular
extensor nuclei; vestibulospinal tract to
muscle tone ipsilateral motor neurons in spinal
cord
Fastigial Influences Fastigial nucleus To neurons of reticular formation;
reticular ipsilateral reticulospinal tract to ipsilateral
muscle tone motor neurons to spinal cord

Cerebellar Syndromes
Vermis Syndrome
The most common cause of vermis syndrome is a medulloblastoma of the vermis in children.
Involvement of the flocculonodular lobe results in signs and symptoms related to the vestibular system.
Since the vermis is unpaired and influences midline structures, muscle in coordination involves the
head and trunk and not the limbs. There is a tendency to fall forward or backward. There is difficulty
in holding the head steady and in an upright position. There also may be difficulty in holding the
trunk erect.
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Cerebellar Hemisphere Syndrome

Tumors of one cerebellar hemisphere may be the cause of cerebellar hemisphere syndrome. The
symptoms and signs are usually unilateral and involve muscles on the side of the diseased cerebellar
hemisphere. Movements of the limbs, especially the arms, are disturbed. Swaying and falling to the side
of the lesion often occur. Dysarthria and nystagmus are also common findings. Disorders of the lateral
part of the cerebellar hemispheres produce delays in initiating movements and inability to move all
limb segments together in a coordinated manner but show a tendency to move one joint at a time.

Dysmetria and Ataxia. Two of the most important symptoms of cerebellar disease are dysmetria and
ataxia. in the absence of the cerebellum, the subconscious motor control system cannot predict how far
movements will go. Therefore, the movements ordinarily overshoot their intended mark; then the
conscious portion of the brain overcompensates in the opposite direction for the succeeding
compensatory movement. This effect is called dysmetria, and it results in uncoordinated movements
that are called ataxia. Dysmetria and ataxia can also result from lesions in the spinocerebellar tracts
because feedback information from the moving parts of the body to the cerebellum is essential for
cerebellar timing of movement termination.
Past Pointing. Past pointing means that in the absence of the cerebellum, a person ordinarily moves
the hand or some other moving part of the body considerably beyond the point of intention. This
results from the fact that normally the cerebellum initiates most of the motor signal that turns off a
movement after it is begun; if the cerebellum is not available to do this, the
movement ordinarily goes beyond the intended mark. Therefore, past pointing is actually a
manifestation of dysmetria.

Dysdiadochokinesia.
Dysdiadochokinesia.

Dysdiadochokinesia is the inability to perform alternating movements regularly and rapidly.

When the motor control system fails to predict where the different parts of the body will be at a given
time, it loses perception of the parts during rapid motor movements. As a result, the succeeding
movement may begin much too early or much too late, so that no orderly progression of movement
can occur. One can demonstrate this readily by having a patient with cerebellar damage turn one hand
upward and downward at a rapid rate. The patient rapidly loses all perception of the instantaneous

9
position of the hand during any portion of the movement. As a result, a series of stalled attempted but
jumbled movements occurs instead of the normal coordinate upward and downward motions. This is
called dysdiadochokinesia

Dysarthria.
Dysarthria Another example in which failure of progression occurs is in talking because the formation
of words depends on rapid and orderly succession of individual muscle movements in the larynx,
mouth, and respiratory system. Lack of coordination among these and inability to adjust in advance
either the intensity of sound or duration of each successive sound causes jumbled vocalization, with
some syllables loud, some weak, some held for long intervals, some held for short intervals, and
resultant speech that is often unintelligible. This is called dysarthria.

Hypotonia.
Hypotonia. Loss of the deep cerebellar nuclei, particularly of the dentate and interposed nuclei, causes
decreased tone of the peripheral body musculature on the side of the cerebellar lesion.

Nystagmus,
Nystagmus which is essentially an ataxia of the ocular muscles, is a rhythmical oscillation of the eyes.
It is more easily demonstrated when the eyes are deviated in a horizontal direction. This rhythmic
oscillation of the eyes may be of the same rate in both directions (pendular nystagmus) or quicker in
one direction than in the other (jerk nystagmus). In the latter situation, the movements are referred to
as the slow phase away from the visual object, followed by a quick phase back toward the target.

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The basal nuclei are a collection of masses of gray matter situated within each cerebral hemisphere.
They are the corpus striatum, the amygdaloid nucleus, and the claustrum.
Clinicians and neuroscientists use a variety of different terminologies to describe the basal nuclei. The
subthalamic nuclei, the substantia nigra are functionally closely related to the basal nuclei, are also
called mescencepalic and diencephalonic basal nuclei.

The basal nuclei play an important role in the control of posture and voluntary movement.

Caudate Nucleus
The caudate nucleus is a large C-shaped mass of gray matter that is closely related to the lateral
ventricle and lies lateral to the thalamus. The lateral surface of the nucleus is related to the internal
capsule, which separates it from the lentiform nucleus .For purposes of description, it can be divided
into a head, a body, and a tail.
The head of the caudate nucleus is large and rounded and forms the lateral wall of the anterior horn of
the lateral ventricle. The head is continuous inferiorly with the putamen of the lentiform nucleus (the
caudate nucleus and the putamen are sometimes referred to as the neostriatum or striatum). Just
superior to this point of union, strands of gray matter pass through the internal capsule, giving the
region a striated appearance, hence the term corpus striatum.
The body of the caudate nucleus is long and narrow and is continuous with the head in the region of
the interventricular foramen. The body of the caudate nucleus forms part of the floor of the body of
the lateral ventricle.
The tail of the caudate nucleus is long and slender and is continuous with the body in the region of the
posterior end of the thalamus. It follows the contour of the lateral ventricle and continues forward in
the roof of the inferior horn of the lateral ventricle. It terminates anteriorly in the amygdaloid nucleus.

Lentiform Nucleus
The lentiform nucleus is biconvex mass of gray matter. It is buried deep in the white matter of the
cerebral hemisphere and is related medially to the internal capsule, which separates it from the caudate
nucleus and the thalamus. The lentiform nucleus is related laterally to a thin sheet of white matter, the
external capsule , which separates it from a thin sheet of gray matter, called the claustrum. The
claustrum, in turn, separates the external capsule from the subcortical white matter of the insula. A
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vertical plate of white matter divides the nucleus into a larger, darker lateral portion, the putamen, and
an inner lighter portion, the globus pallidus. The paleness of the globus pallidus is due to the presence
of a high concentration of myelinated nerve fibers. Inferiorly at its anterior end, the putamen is
continuous with the head of the caudate nucleus.

Functional Consideration.

The caudate and putamen have similar functions, structure and morphology so together the caudate
and putamen are called the neostriatum or simply striatum . All input to the basal ganglia circuit
comes via the striatum. This input comes mainly
from motor cortical areas.

Globus Pallidus a medial part of the part of the lentiform nucleus is called paleo striatum or simply
pallidum. is actually the output system of the basal nuclei.

Basal Nuclei Pathways.

The direct pathway and the indirect pathway. These two pathways have opposite
effects on motor activity and help explain many clinical symptoms of basal ganglia diseases.

Both of these pathways functions parallel to each other with slightly antagonistic to each other by
phenomenon known as "disinhibition".

In the direct pathway, striatal cells project directly to GP-i(internal segment). The consequence of this
pathway is to increase the excitatory drive from thalamus to cortex.

The cortical projections to the striatum use the excitatory transmitter glutamate. When they are
activated, these cortical projections excite striatal neurons. This excitatory input is enough to turn on

12
the striatal cell. This striatal cell uses the inhibitory transmitter GABA and its axon passes to, and
inhibits, a cell in GP(internal). The cells in GP-i(internal)that project to VA/VL also use GABA. So,
the cortical signal excites striatal neurons, which results in MORE inhibition from striatum to
GP(internal). More inhibition of GP(internal) means LESS inhibition of motor thalamus(VA/VL).Since
the motor thalamus receives LESS inhibition, the VA/VL cells will INCREASE their firing(VA/VL (VA/VL cells
inputs))
are not just receiving the inhibitory pallidal input, but have other excitatory inputs
[one source you know is cerebellar excites the VA and VL].
This decrease in inhibition is called dis-
dis-inhibition.Though
inhibition not the same as direct excitation, it similarly
leads to an increase in activity. So the end result of cortical excitatory input to striatal neurons at the
head of the direct pathway is INCREASED FIRING OF VA/VL NEURONS AND IN TURN
MOTOR CORTEX.

REMEMBER, THE DIRECT PATHWAY TURNS UP (EXCITES) MOTOR ACTIVITY

Indirect Pathway

In Indirect Pathway Instead of projecting to GP-i(internal), the striatal

neurons of the indirect pathway project to GP-e(external)

Cells in GP-e(external) project to the subthalamic nucleus. Cells in the subthalamic nucleus then
project to GP(internal), which in turn projects to VA/VL. So, the indirect pathway is striatum to
GP(external) to subthalamic nucleus to GP-i(internal) to VA/VL to motor cortex.

In the indirect pathway, cortical fibers excite striatal neurons that project to GP-e(external). The
increased activity of the GABAergic striatal neurons decreases activity in GP-e (external). The
GABAergic cells in GP-e(external) inhibit cells in the subthalamic nucleus, so the decrease in activity
in GP-e(external) results in less inhibition of cells in the
subthalamic nucleus. That is, subthalmic neurons are dis-inhibited and increase their activity. The
return projection from the subthalamic nucleus to GP-i(internal) is excitatory, so the

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increased activity in the subthalamic nucleus results in more excitation to cells in GP-i (internal). Thus,
the end result of actions of the indirect loop is an increase in activity of the GABAergic cells in GP-
i(internal) that project to VA/VL or an
INCREASE in INHIBITION of the thalamic neurons

The Indirect Pathway turns DOWN the motor thalamus and, in turn, motor cortex. Thus,
it TURNS DOWN motor activity.

DOPAMINERGIC and CHOLINERGIC effect on Direct and Indirect Pathways

In addition to GABAergic and Glutenergic pathway what we have seen earlier, striatal neurons are also
modulated by two important neuromodulatory systems. Each of these systems differentially affects the
direct and indirect pathways, thereby altering their balance and the amount of motor activity that is
produced.

DOPAMINE Pathway
Dopamine is produced by cells in the pars compacta of the substantia nigra (SNc).
Nigrostriatal axon terminals release dopamine into the striatum. Dopamine has an
EXCITATORY effect upon cells in the striatum that are part of the Direct Pathway. This is via
D1receptors.
D1receptors
Dopamine has an INHIBITORY effect upon striatal cells associated with the Indirect Pathway. This is
via D2 receptors.
receptors In other words, the direct pathway (which turns up motor activity) is excited by
dopamine while the indirect pathway (which turns down motor activity) is inhibited. Both of these
effects lead to increased motor activity

"DOPAMINE EXCITES THE DIRECT AND INHIBITS THE INDIRECT PATHWAY"

PATHWAY"

Cholinergic Pathway

There is a population of cholinergic(ACh) neurons in the striatum whose axons do not leave the
striatum(called inter neurons or local circuit neurons). These cholinergic interneuron's synapse on the

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GABAergic striatal neurons that project to GP-i(internal) AND on the striatal neurons that project to
GP-e(external). The cholinergic actions INHIBIT striatal cells of the
Direct pathway and EXCITE striatal cells of the Indirect pathway. Thus the effects of ACh are
OPPOSITE the effects of dopamine on the direct and indirect pathways so the ACh effects on motor
activity are opposite those of dopamine.

"ACh INHIBITS THE DIRECT AND EXCITES THE INDIRECT PATHWA

PATHWAYY"

Disorders of the Basal Ganglia:

Damage to the basal ganglia causes two different classes of syndromes, one characterized by an
increase in movement (hyperkinetic) and the other characterized by decreased movement
(hypokinetic). The most well known hypokinetic syndrome is Parkinsons disease, and it generally
affects the elderly population. While hypokinesia (reduced movement) is the hallmark of Parkinsons
disease, three other signs (rigidity, tremor and loss of postural reflexes) accompany this decrease in
movement.

In Parkinsons disease, rigidity is present in all muscle groups, both flexor and extensor, so
that the resistance to passive movement is intense and consistent through the entire range of
motion,so-called lead-pipe rigidity. This is often accompanied by cogwheeling, which refers to jerky,
ratchet-like movements of the joints. Unlike the spasticity linked to upper motor neuron lesions, there
is no change in the tendon reflexes and all muscles are affected although there is a tendency for the
patients to maintain a flexed posture in both arms and legs. The tremor of Parkinsons patients is a
static or resting tremor, which refers to the involuntary 4-5 Hz movements when the limb is held at
rest but disappears during a voluntary movement. This contrasts sharply with the intention tremor of
cerebellar signs. The loss of postural reflexes results in balance problems, which can manifest as
unstable, stooped, or slumped-over posture and a shuffling walk of small steps followed by the need for
quicker steps to maintain balance. It is difficult to explain all these symptoms with the knowledge that
we currently have, but we can certainly account for the hypokinesia.

As you know, dopaminergic neurons in substantia nigra pars compacta are lost in Parkinsons disease.
The degenerating nigral dopaminergic cells accumulate deposits of protein called Lewy Bodies . This is
a histological hallmark of the disease.

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Since the hypokinetic (Parkinsons) patients have decreased levels of dopamine in the
striatum and substantia nigra pars compacta, they can be treated symptomatically with
dopaminergic agonists, such as L-dopa. This is a precursor of dopamine that crosses the blood brain
barrier. Parkinsons patients can also be treated with drugs that decrease the level of acetylcholine in
the striatum.

Hyperkinetic Disorders of the Basal Ganglia:

While the loss of dopamine from the substantia nigra results in hypokinetic symptoms seen
in Parkinsons disease, hyperkinetic problems are caused by other pathologies of the basal
ganglia. Two classic hyperkinetic disorders are hemiballism and Huntingtons chorea.
Hemiballism is characterized by wild, flinging movements of the body, and it results from
lesion in the subthalamic nucleus. The excitatory input to GP-i(internal) is lost
following such lesions. The result is LESS inhibition reaching the VA/VL (the subthalamic
nucleus normally increases the inhibition in the pallidal-VA/VL projection). Thus, the VA/VL is
turned up, as is motor cortex, and there is uncontrollable hyperactivity of the motor system.

Huntingtons chorea
Huntingtons chorea is characterized by involuntary choreiform movements which show
up as rapid, involuntary and purposeless jerks of irregular and variable location on the body. They are
spontaneous and cannot be inhibited, controlled, or directed by the patient. Huntingtons chorea is an
inherited disease that usually shows up at the age of 40. Disease onset is slow and hard to diagnose,
but usually general irritableness and explosive behavior precede motor symptoms. Later, there is
memory loss and attention deficit, followed by restless or fidgety hands. Finally, the disease progresses
with facial movements and constant jerky movements of all parts of the body. Despite the continual
movements, there may be hypotonia. The initial cause of these uncontrollable movements is the loss
of GABAergic cells in the striatum that project only to GP-e(external), the head of the indirect
pathway. This loss shows up on MRI as degeneration in the caudate nucleus. The loss of this inhibition
on the head of the indirect pathway (which turns down motor activity) means that VA/VL is turned
up, as is the motor cortex, and there is uncontrollable hyperactivity of the motor system. In addition to

16
the loss of striatal GABAergic cells of the indirect pathway, the striatal cholinergic cells also begin to
die . The loss of both types of cell causes less inhibition of VA/VL and increased motor output

Athetosis
Athetosis consists of slow, sinuous, writhing movements that most commonly involve the distal
segments of the limbs. Degeneration of the globus pallidus occurs with a breakdown of the circuitry
involving the basal nuclei and the cerebral cortex.

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