Abstract:

The basal ganglia (BG) assemble a series of deep gray matter structures forming recurrent loops that include the cortex and thalamus, and that participate in the regulation of a plethora of brain functions, including elicitation and learning of reward-and aversive stimuli-associated behaviors,motor activity control and sensorimotor gating (Bromberg-Martin et al., 2010). The striatum is the main input BG structure, thus it receives cortical glutamatergic projections from widespread areas of cortex and projects into other BG nuclei, including globus pallidus pars externa and the BG outputsglobus pallidus pars interna and substantia nigra pars reticulata. On the other hand, the substantia nigra pars compacta-ventral tegmental area (SNpc-VTA) modulates cortical-BG-thalamic circuits by means of dopaminergic innervation of the striatum. Interestingly, the main population of striatal neurons, the medium spiny neurons (MSNs),provide the origin of two different striatal efferent pathways,the direct and indirect pathways (Schiffmann et al., 2007).Both project to the BG outputs, and the direct pathway also projects to brainstem, to the SNpc-VTA. The MSN originating these two pathways are characterized by the differential expression of several key genes. Thus, while MSNs from the direct pathway (direct MSNs) express dopamine D1 receptors (D1R) and contain the neuropeptides dynorphin and substance P, indirect MSNs express dopamine D2 receptors (D2R) and contain the neuropeptide enkephalin (Fuxe et al.,2007; Schiffmann et al., 2007). Striatal dopamine from SNpc-VTA projections potentiates direct and inhibits indirect pathway MSN, which leads to a net inhibition of thalamocortical areas.