Dopamine and cholinergic effects

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In addition to the GABA neurons, two other sources of chemically significant neurons enhance the effects of the direct or indirect pathways.

Dopaminergic neurons in the substantia nigra in the midbrain project to the striatum. The effect of dopamine excites or drives the direct pathway, increasing cortical excitation. Dopamine excites the direct pathway through D( receptors and inhibits the indirect pathway through D2 receptors.

Cholinergic neurons found within the striatum have the opposite effect. Acetylcholine drives the indirect pathway, decreasing cortical excitation.

Plane of section

Plane of section

Lateral Ventricle Anterior Horn

Figure IV-9-2.The Basal Ganglia

Corpus callosum

Lateral ventricle

Caudate nucleus

Putamen

Globus pall id us

Thalamus

Third ventricle

Figure IV-9-2.The Basal Ganglia

Table IV-9-1. Basal Ganglia—Clinicopathologic Correlations

Movement Disorder

Lesion

Chorea: muldple quick, random movements, usually most prominent in the appendicular muscles

Atrophy of the striatum. Huntington chorea.

Athetosis: low writhing movements, which are usually more severe in the appendicular muscles

Diffuse hypermyelinization of the corpus striatum and thalamus cerebral palsy.

Hemiballismus: wild flinging movements of half of the body

Hemorrhagic destruction of the contralateral' subthalamic nucleus. Hypertensive patients.

Parkinsonism: pill-rolling tremor of the fingers at rest, lead-pipe rigidity, and akinesia

Degeneration of the substantia nigra

Clinical Correlate

Lesions or Diseases of the Basal Ganglia

Lesions or diseases of the basal ganglia generally present with movement disorders, known as i dyskinesias, and an involuntary tremor, or tremor at rest

Most basal ganglia disorders seem to preferentially affect either the direct or the indirect pathways, altering the balance between the two.

Lesions of the direct pathway

Lesions of the direct pathway result in an underactive cortex and hypokinetic disturbances in which there is a slowing or absence of spontaneous movements. The best known disorder of the direct pathway is caused by the degeneration of dopaminergic neurons of the substantia nigra in Parkinson disease. Because the cortex is underactive, Parkinson patients have problems initiating movements, combined with a reduction in the velocity and amplitude of the movements. The tremor at rest is the classic pill rolling tremor seen in the fingers. Skeletal muscles in the upper limbs exhibit a cog wheel rigidity because of increased muscle tone. Patients also present with a stooped posture, an expressionless face, and a festinati'ng or accelerating gait during which individuals seem to chase their center of gravity. One strategy for Parkinson patients is to give them L-dopa, a dopamine precursor that crosses the blood-brain barrier. Another strategy is to give anticholinergic drugs to inhibit the effects of acetylcholine on the indirect pathway.

Lesions of the indirect pathway

Other common disorders of the basal ganglia (chorea, athetosis, dystonia, tics) result from lesions to parts of the indirect pathway, which result in an overactive motor cortex. An overactive cortex produces hyperkinetic disturbances, expressed in numerous spontaneous movements. The involuntary tremors -seen in these diseases range from being dancelike in chorea to ballistic with lesions to the subthalamic nucleus.

Chorea produces involuntary movements that are purposeless, quick jerks that may be superimposed on voluntary movements. Huntington chorea exhibits autosomal dominant inheritance (chromosome 4) and is characterized by severe degeneration of GABA neurons in the striatum. In addition to chorea, these patierrts frequently suffer from athetoid movements, progressive dementia, and behavioral disorders. Sydenham chorea is a transient complication in some children with rheumatic fever.

Athetosis refers to slow, wormlike, involuntary movements that are most noticeable in the fingers and hands but may involve any muscle group. It is present in Huntington disease and may be observed in many diseases that involve the basal ganglia.

Dystonia refers to a slow, prolonged movement involving predominantly the truncal musculature. Dystonia often occurs with athetosis. Blepharospasm (contraction of the orbicularis oculi causing the eyelids to dose), spasmodic torticollis (in which the head is pulled toward the shoulder), and writers cramp (contraction of arm and hand muscles on attempting to write) are all examples of dystonic movements.

Hemiballismus results from a lesion of the subthalamic nucleus usually seen in hypertensive patients. Hemiballismus refers to a violent projectile movement of a limb and is typically observed in the upper limb contralateral to the involved subthalamic nucleus.

(Continued)

Clinical Correlate (continued)

Tourette syndrome involves facial and vocal tics that progress to jerking movements of the limbs. It is frequently associated with explosive, vulgar speech.

Wilson disease results from an abnormality of copper metabolism, causing the accumulation of copper in the liver and basal ganglia. Personality changes, tremor, dystonia, and athetoid movements develop. Untreated patients usually succumb because of hepatic cirrhosis. A thin brown ring around the outer cornea, the Kayser-Fleischer ring, may be present and aid in the diagnosis.

Chapter Summary

The basal ganglia play important motor functions in starting and stopping voluntary motor functions and inhibiting unwanted movements. The basal ganglia consists of three nuclei masses deep in the cerebrum (caudate nucleus, putamen, and globus pallidus), one nucleus in the midbrain (substantia nigra), and the subthalamic nucleus of the diencephalon. The striatum combines the caudate nucleus and the putamen while the corpus striatum consists of these two nuclei plus the globus pallidus.

There are two parallel circuits (direct and indirect) through the basal ganglia. These circuits receive extensive input from the cerebral cortex that project back to the motor cortex after a relay in the VL nucleus of the thalamus. Both of these pathways demonstrate disinhibition. The direct pathway increases the level of cortical excitation and promotes movement The indirect pathway decreases the level of cortical excitation and stops movement.

The striatum is the major input center and the globus pallidus is the major output center for the pathways through the basal ganglia. Critical to proper function of the striatum is dopamine production by the substantia nigra. Dopamine excites the direct pathway and inhibits the indirect pathway.

Lesions of the direct pathway result in an underactive cortex, which produces hypokinetic motor disturbances. The classic disorder caused by degeneration of dopaminergic neurons of the substantia nigra is Parkinson disease. These patients are characterized by tremor at rest (pill-rolling), increased muscle tone, mask face, and hypokinetic movement

Hyperkinetic disorders result from lesions of the indirect pathway and cause an overactive motor cortex. These movements occur spontaneously at rest and cannot be controlled by the patient. Examples of these disorders include chorea (multiple quick movements), athetosis (slow serpentine movements), and hemiballismus (violent flinging movements). Hemiballismus results from hemorrhagic destruction of the contralateral subthalamic nucleus.

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