Chapter 8C - The Basal Ganglia
The extrapyramidal system consists of a series of functionally related nuclei in the telencephalon, diencephalon and midbrain. The basal ganglia represent the largest component, and include the caudate, putamen and globus pallidus. The pars reticulata and pars compacta of the substantia nigra of the midbrain as well as the subthalamic nucleus, which is located in the caudal diencephalon are functionally connected to this system.
The caudate and putamen are functionally and histologically similar nuclei located on either side of the internal capsule. Collectively, they are called the striate nuclei, the neostriatum or the striatum. The caudate nucleus is on the ventrolateral side of the lateral ventricle. The caudate has a very large head with a body that follows most of the sweep of the lateral ventricle. The tail enters the temporal lobe with the temporal horn of the lateral ventricle. The globus pallidus, is immediately medial to the putamen and has a medial and lateral segment. Collectively, the putamen and globus pallidus are termed the lenticular or lentiform nuclei. There's a small rind of cells called the claustrum which is separated from the putamen by the external capsule and from the insular cortex by the extreme capsule.
The extrapyramidal system has historically been viewed as a part of the motor system, since damage to these areas affect muscle tone, posture, voluntary movements and can also produce abnormal movements. It has become increasingly clear that this system is also used for control of behavioral "tone" and emotional "posture" of the animal as a whole. This will be discussed toward the end of this section. Most of our discussion will focus on motor systems, since that has been studied best and since the lessons learned from the effect on movement may be applicable to understanding involvement in emotions and behaviors.
Fundamentally, the principal connections made by the extrapyramidal system are via closed circuits that receive input from the cerebral cortex and project reciprocally back to the cerebral cortex (figure 25). When considering the motor functions of the extrapyramidal system, the greatest input arises from the premotor cortex. This portion of the cortex is most involved in planning, patterning and initiating movements. The circuit passes through several nuclei in the system, each of which is involved in processing.
There are two described pathways for transmission of signals through the basal ganglia, a direct and an indirect pathway (figure 25). These pathways have competing effects on movement and there is often thought to be a balance between these systems that is involved in establishing and regulating tone. In both the direct and indirect pathways, the caudate and putamen represent the first synapse in the system. These nuclei receive afferent nerve fibers from virtually all portions of the cerebral cortex, but especially from the premotor areas. The caudate and putamen also receive input from the intralaminar nuclei of the thalamus as well as from several neurotransmitter systems that modulate the activity of the neurons. For example, the substantia nigra pars compacta provides critically important dopaminergic innervation and several raphe nuclei give rise to serotonin input to the basal ganglia. Therefore, drugs that affect these transmitter systems can have major effects on movement.
Output from the striatum is all via GABAergic, inhibitory neurons. The striatum projects to the medial and lateral segments of the globus pallidus as well as to the substantia nigra, pars reticulata. This latter nucleus is best thought of as a functional part of the globus pallidus since its neurons have similar inputs and response characteristics to those of the globus pallidus.
The globus pallidus, itself, has two components, a medial (internal) and lateral (external) segment. The globus pallidus has an interesting physiology since its output is solely via inhibitory GABAergic neurons that are tonically active. Therefore, in the absence of any input, there would be a tonic inhibitory signal arising from these neurons. The lateral or external segment of the globus pallidus is a part of the indirect pathway, while the medial segment is a component in both the direct and indirect pathways. We will first discuss the direct pathway and then the indirect.
In the direct pathway (figure 25), cerebral cortical input to the striatum activates the inhibitory projection neurons in the striatum. This increases the inhibitory output to the tonically active medial globus pallidus. The output of the medial globus pallidus is to the ventral anterior and ventrolateral nucleus of the thalamus via two pathways. The lenticular fasciculus cuts through the internal capsule while the ansa lenticularis courses ventral to the internal capsule. These two pathways meet at the thalamic fasciculus and terminate in the thalamus in two adjacent regions, the ventral anterior nucleus (VA) and the rostral part of the ventral lateral nucleus (VL). The VA and VL of the thalamus project via excitatory pathways primarily to the premotor cerebral cortex. This feedback is involved in regulating the tonic level of excitation in the premotor cortex, an area involved in planning and initiating of movement.
In considering the physiology of the direct pathway, note that the cortical input to the striatum would excite the inhibitory projection neurons to the medial globus pallidus. This would decrease activity in the tonically active projection neurons in the medial globus pallidus and, in turn, would decrease the tonic inhibitory pressure on the VA and VL of the thalamus. Ultimately, there would be disinhibition of thalamic excitation of the cerebral cortex. In other words, this pathway results in a net facilitation of the cerebral cortex. In the case of the motor cortex, activation of the direct pathway would increase the ease of movement and of initiating movement.
The indirect pathway (figure 25) is inhibitory to movement. Excitatory projections from the cerebral cortex facilitates inhibitory projection neurons in the striatum. These project to the lateral (external) globus pallidus where they inhibit the tonic inhibitory output neurons. This decreases tonic inhibition of the subthalamic nucleus, resulting in increased excitatory output to the medial globus pallidus. The subthalamic nucleus is a small collection of excitatory neurons located at the junction between the midbrain and diencephalons. This excitatory input to the medial globus pallidus increases the inhibitory output from the medial globus pallidus to the thalamus, ultimately decreasing the excitatory feedback to the cerebral cortex. Note that the indirect pathway has opposite effects on the medial segment of the globus pallidus than does the direct pathway. Ultimately, the indirect pathway is inhibitory to motor cortical activity.
Dopamine projections from the substantia nigra, pars compacta, to the striatum have complex, and ultimately opposing effects on activity in the direct and indirect pathways (figure 25). For example, dopamine acts primarily through dopamine D1 receptors on the neurons that participate in the direct pathway, exciting these neurons. It acts on dopamine D2 receptors on the striatal neurons that are involved in the indirect pathway. The D2 receptors are inhibitory. Therefore, dopamine excites the direct pathway and inhibits the indirect pathway, with a net effect to increase facilitatory inputs to the motor regions.
Most of the output from the basal ganglia goes through the thalamus to the cerebral cortex, effecting movement by influencing motor cortex activity. However, there are some other outputs from the basal ganglia. The striatum projects to the substantia nigra pars reticulata. Just like the globus pallidus the substantia nigra reticulata contains tonically active GABAergic output neurons. Efferent projections from the reticulata project to several places. These include the dorsomedial thalamic nucleus that feeds back on several cerebral cortical sites, particularly those effecting motivation and mood. Also, the reticulata projects directly to the brain stem reticular formation (affecting muscle tone) and to the superior colliculus (affecting eye movements). Altered activity in this system can be seen as the slow and irregular eye movements seen in patients with Parkinson's disease.
The extrapyramidal system is involved in setting the level of external responsiveness to stimuli and also in establishing tones and postures of the body. Many neurons in the basal ganglia begin to show activity before movement actually takes place. These have been termed "getting set cells." Additionally, damage to the basal ganglia can result in abnormal involuntary movements, termed dyskinesias. These movements can take several forms that may give clues as to the cause of the abnormality.
It has become increasingly apparent that the basal ganglia are involved in more than motor control. Recent attention has been directed to the mesolimbic dopamine reward system, an important system for the control and reinforcement of behavior (figure 26). There is a system that has many similarities to the direct pathway that we have previously described. It is primarily involved in controlling emotional tones and responsiveness to the world. This system has also been termed the ventral striatal system and begins with projections from emotional portions of the cerebral cortex, often termed the limbic cortex, to the ventral striatum. This is located where the head of the caudate and the putamen meet, called the nucleus accumbens. The nucleus accumbens projects to the ventral pallidum, a region that is immediately ventral to the anterior commissure in the basal forebrain. Note that it is close to the globus pallidus. The ventral pallidum projects to the dorsomedial nucleus of the thalamus, which, in turn, projects to the limbic areas of the cerebral cortex. These areas are important for maintaining behavioral tone and motivation. In most respects this pathway is similar to the direct pathway which results in increased thalamic feedback to the cerebral cortex. Just like the direct pathway, dopamine is important in increasing activity in striatal neurons. In this case, the dopamine input derives from the ventral tegmental area, which is located in the ventromedial aspect of the midbrain. It appears to act primarily on the D3 subtype of dopamine receptor. This dopamine system appears to be stimulated by most drugs of abuse and may be over active in schizophrenia.