Basal Ganglia Anatomy, Biochemistry, and Physiology

Circuits

The basal ganglia include the striatum (caudate, putamen, nucleus accumbens), the subthalamic nucleus (STN), the globus pallidus (internal segment—GPi, external segment—GPe, ventral pallidum—VP), and the substantia nigra (pars compacta—SNpc and pars reticulata—SNpr) ( Fig. 1.1 ). The striatum and STN receive the majority of inputs from outside of the basal ganglia. Most of those inputs come from cerebral cortex, but thalamic nuclei also provide strong inputs to striatum. The bulk of the outputs from the basal ganglia arise from the globus pallidus internal segment, VP, and substantia nigra pars reticulata. These outputs are inhibitory to the pedunculopontine area in the brainstem and to thalamic nuclei that in turn project to frontal lobe.

The striatum receives the bulk of extrinsic input to the basal ganglia. The striatum receives excitatory input from virtually all of cerebral cortex. In addition, the ventral striatum (nucleus accumbens and rostroventral extensions of caudate and putamen) receives inputs from hippocampus and amygdala. The cortical input uses glutamate as its neurotransmitter and terminates largely on the heads of the dendritic spines of medium spiny neurons. The projection from the cerebral cortex to striatum has a roughly topographic organization that provides the basis for an organization of functionally different circuits in the basal ganglia. ^, Although the topography implies a certain degree of parallel organization, there is also evidence for convergence and divergence in the corticostriatal projection. The large dendritic fields of medium spiny neurons allow them to receive input from adjacent projections, which arise from different areas of cortex. Inputs to striatum from several functionally related cortical areas overlap and a single cortical area projects divergently to multiple striatal zones. ^, Thus, there is a multiply convergent and divergent organization within a broader framework of functionally different parallel circuits. This organization provides an anatomical framework for the integration and transformation of cortical information in the striatum.

Cell Types

Medium spiny striatal neurons make up 90%–95% of the striatal neuron population. They project outside of the striatum and receive a number of inputs in addition to the important cortical input, including (1) excitatory glutamatergic inputs from thalamus; (2) cholinergic input from striatal interneurons; (3) gamma-amino-butyric acid (GABA), substance P, and enkephalin input from adjacent medium spiny striatal neurons; (4) GABA input from fast-spiking interneurons; (5) a large input from dopamine-containing neurons in the SNpc; (6) a more sparse input from the serotonin-containing neurons in the dorsal and median raphe nuclei.

The fast-spiking GABAergic striatal interneurons make up only 2%–4% of the striatal neuron population, but they exert powerful inhibition on medium spiny neurons. Like medium spiny neurons, the striatal interneurons receive excitatory input from cerebral cortex. They appear to play an important role in limiting the activity of medium spiny neurons and in focusing the spatial pattern of their activation. Abnormalities in the number or function of these neurons have been linked to the pathobiology of involuntary movements.

Compartments

Although there are no apparent regional differences in the striatum based on cell type, an intricate internal organization has been revealed with special stains. When the striatum is stained for acetylcholinesterase (AChE), there is a patchy distribution of lightly staining regions within more heavily stained regions. The AChE-poor patches have been called striosomes and the AChE-rich areas have been called the extrastriosomal matrix . The matrix forms the bulk of the striatal volume and receives input from most areas of cerebral cortex. Within the matrix are clusters of neurons with similar inputs that have been termed matrisomes . The bulk of the output from cells in the matrix is to both segments of the GP, VP, and to SNpr. The striosomes receive input from prefrontal cortex and send output to SNpc. Immunohistochemical techniques have demonstrated that many substances such as substance P, dynorphin, and enkephalin have a patchy distribution that may be partly or wholly in register with the striosomes. The striosome-matrix organization suggests a level of functional segregation within the striatum that may be maintained by differential influences of dopamine. While preferential involvement of the striosome or matrix compartments has been suggested in some disorders, the clinical significance of this organization is still not well understood.