The functional anatomy ofdisorders of the basal ganglia.

Thus, as a result of the complex sequences of excitation, inhibition, and disinhibition, the net effect of the cortex exciting the direct pathway is to further excite the cortex (positive feedback loop), whereas the net effect of cortex exciting the indirect pathway is to inhibit the cortex (negative feedback loop). Presumably, the function of the basal ganglia is related to a proper balance between these two pathways. Motor cortex neurons have to excite the proper direct pathway neurons to further increase their own firing, and they have to excite the proper indirect pathways neurons that will inhibit other motor cortex neurons that are not adaptive for the task at hand (see below).

Network models of the basal ganglia.

 Gross Anatomy of the Basal Ganglia

The basal ganglia: A vertebrate solution to the selection problem?

There are two distinct pathways that process signals through the basal ganglia: the direct pathway and the indirect pathway. These two pathways have opposite net effects on thalamic target structures. Excitation of the direct pathway has the net effect of exciting thalamic neurons (which in turn make excitatory connections onto cortical neurons). Excitation of the indirect pathway has the net effect of inhibiting thalamic neurons (rendering them unable to excite motor cortex neurons). The normal functioning of the basal ganglia apparently involves a proper balance between the activity of these two pathways. One hypothesis is that the direct pathway selectively facilitates certain motor (or cognitive) programs in the cerebral cortex that are adaptive for the present task, whereas the indirect pathway simultaneously inhibits the execution of competing motor programs. An upset of the balance between the direct and indirect pathways results in the motor dysfunctions that characterize the extrapyramidal syndrome (see below).

Functional and pathophysiological modelsof the basal ganglia.

The indirect pathway starts with a different set of cells in the striatum. These neurons make inhibitory connections to the external segment of the globus pallidus (GPext). The GPext neurons make inhibitory connections to cells in the subthalamic nucleus, which in turn make excitatory connections to cells in the GPint. (Remember that the subthalamic-GPint pathway is the only purely excitatory pathway within the intrinsic basal ganglia circuitry.) As we saw before, the GPint neurons make inhibitory connections on the thalamic neurons. To see the net effects of activation of the indirect pathway, let us work backwards from the GPint. When the GPint cells are active, they inhibit thalamic neurons, thus making cortex less active. When the subthalamic neurons are firing, they increase the firing rate of GPint neurons, thus increasing the net inhibition on cortex. Firing of the GPext neurons inhibits the subthalamic neurons, thus making the GPint neurons less active and disinhibiting the thalamus. However, when the indirect pathway striatal neurons are active, they inhibit the GPext neurons, thus disinhibiting the subthalamic neurons. With the subthalamic neurons free to fire, the GPint neurons inhibit the thalamus, thereby producing a net inhibition on the motor cortex.

Which of the basal ganglia nuclei receive direct cortical input?

In the motor regions of the basal ganglia, there is a motor homunculus similar to that seen in the primary motor cortex. Thus, the projections from the medial wall of the anterior paracentral lobule (the part of M1 that contains a representation of the legs and torso) innervate regions of the striatum that are next to the recipient zones from the dorsal surface of the precentral gyrus (the part of M1 that contains a representation of the arms and hands). Similarly, the projections from the lateral surface of the precentral gyrus (the part of M1 that contains a representation of the face) innervate regions that are next to the arm and hand representation. This topography of projections is maintained in the intrinsic circuitry of the basal ganglia.

Which of the basal ganglia nuclei receive direct cortical input?

The striatum is the main recipient of afferents to the basal ganglia (Figure 4.2). These excitatory afferents arise from the entire cerebral cortex and from the intralaminar nuclei of the thalamus (primarily the centromedian nucleus and parafascicularis nucleus). The projections from different cortical areas are segregated, such that the frontal lobe projects predominantly to the caudate head and the putamen; the parietal and occipital lobes project to the caudate body; and the temporal lobe projects to the caudate tail. The primary motor cortex and the primary somatosensory cortex project mainly to the putamen, whereas the premotor cortex and supplementary motor areas project to the caudate head. Other cortical areas project primarily to the caudate. Thus, along the C-shaped extent of the caudate nucleus, the caudate cells receive their input from the cortical regions that are close by. The enlarged head of the caudate reflects the large projection from the frontal cortex to the caudate. In addition, the nucleus accumbens (ventral striatum) receives a large input from limbic cortex.

Which of the basal ganglia nuclei receive direct cortical input?

Recall that the major output from the basal ganglia is an inhibitory connection from the GPint (or SNr) to the thalamus (or superior colliculus). Studies of eye movements in monkeys have shed light on the function of the basal ganglia loop. Normally, the SNr neurons are tonically active, suppressing the output of the collicular neurons that control saccadic eye movements. When the direct pathway striatal neurons are excited by the cortical frontal eye fields, the SNr neurons are momentarily inhibited, releasing the collicular neurons from inhibition. This allows the appropriate collicular neurons to signal the target of the eye movement, allowing the monkey to change its gaze to a new location. The movement was initiated in the frontal eye fields; however, the proper activation of the eye movement required that collicular neurons be released from the inhibition of the basal ganglia.