Basal Ganglia: Internal Organization

The basal ganglia are a group of subcortical nuclei involved in a variety of processes, including motor, associative, cognitive, and mnemonic functions. The dorsal division of the basal ganglia consists of the striatum (divided into the caudate nucleus and putamen by the internal capsule in primates and other species), the external segment of the globus pallidus (GPe; simply globus pallidus in rodents), the internal segment of the globus pallidus (GPi; entopeduncular nucleus (EP) in several species, including rodents and cats), the subthalamic nucleus (STN), and the substantia nigra (SN). The latter structure is divided into two main parts, the dorsal pars compacta (SNc), in which the dopaminergic nigrostriatal neurons are located, and the more ventral pars reticulata (SNr). In addition to these structures that are associated with motor and associative functions of the basal ganglia, there is a ventral division of the basal ganglia (ventral striatum or nucleus accumbens; ventral pallidum, which is equivalent to GPe and GPi; and the ventral tegmental area, which is a medial continuation of the SNc). The ventral division of the basal ganglia is primarily associated with limbic functions. The nomenclature of divisions of the basal ganglia can be particularly confusing to a reader new to the field. For this reason a table (Table 1) of commonly used terms and their synonyms or homologous structures is included. The main transmitter used by neurons of the basal ganglia is g-aminobutyric acid (GABA); as many as 99% of all basal ganglia neurons are GABAergic. The only exceptions are glutamatergic neurons of the STN, dopamine neurons of the SNc, and one population of interneurons in the striatum that utilizes acetylcholine. The major inputs to the basal ganglia are glutamatergic and are derived from the cerebral cortex and the thalamus. The main point of entry of the cortical and thalamic information to the basal ganglia is the striatum, although there are also significant projections to the STN (Figure 1). Virtually the entire cortical mantle projects onto the striatum. The corticostriatal projection is derived from several classes of cortical pyramidal neurons that predominantly innervate the ipsilateral striatum but also the contralateral striatum. The corticosubthalamic projection is derived from more restricted regions of the cortex (see below). The corticostriatal and thalamostriatal projections are highly topographically organized and impart functionality onto the striatum and, consequently, other divisions of the basal ganglia. The main synaptic targets of the cortical and thalamic inputs to the basal ganglia are the medium-sized densely spiny projection neurons of the striatum ( Figures 2 and 3 ). In what is now considered the classical view of basal ganglia circuitry, the functional organization is such that cortical and thalamic information is processed within the striatum and integrated with the many other inputs that reach the basal ganglia (e.g., from amygdala, hippocampus, and dorsal raphé), which primarily innervate the striatum, and then the ‘processed information’ is transmitted to the output nuclei of the basal ganglia, that is, the GPi (or EP) and the SNr, by two routes, the so-called direct and indirect pathways. In the direct pathway, cortical and thalamic information is transmitted directly from the striatum to the output nuclei. In the indirect pathway, cortical and thalamic information is transmitted indirectly to the output nuclei via the complex network interconnecting the GPe and STN. The basal ganglia then influence behavior by projecting, via the output nuclei, to the thalamus (mainly the ventral anterior and ventral lateral nuclear complex, mediodorsal nucleus and the intralaminar nuclei) that in turn projects back to the cortex or by projecting to subcortical regions that are involved in movement, including the superior colliculus, the pedunculopontine nucleus (PPN), lateral habenula, and reticular formation (Figure 1). Overlying this feed-forward organization of the basal ganglia are many feedback pathways. The major one of these is the dopaminergic projection from the SNc that predominantly innervates the striatum but also innervates the STN and GPe. This projection modulates the flow of cortical and thalamic information through the basal ganglia. Loss of these dopamine neurons in Parkinson’s disease leads to an imbalance of the flow of cortical information through the basal ganglia in favor of the indirect pathway and the motor symptoms associated with this disorder. Other feedback systems include the serotonergic projection from the dorsal raphé and the projection from the GPe to striatum (see later). Basal Ganglia: Internal Organization 97