The three C-BG-C circuits on which we will focus share a basic cellular and molecular connectivity (Dudman and Gerfen 2015). Cortical regions send glutamatergic projections striatum that innervate both GABAergic medium spiny projection neurons (MSNs) and striatal interneurons. Specific thalamic subregions also send glutamatergic inputs to the MSNs and striatal interneurons. The striatum also receives dense dopaminergic projections from the midbrain, and much sparser monoaminergic inputs from other hindbrain regions that vary in different striatal subregions (Molliver 1987, Berridge, Stratford et al. 1997, Delfs, Zhu et al. 1998). The MSNs then send GABAergic projections to the GPe, GPi and SNr. Projections to GPi/SNr comprise the “direct” pathway that activates cortical output, while projections targeting the GPe via the “indirect” pathway inhibit cortical output. GABAergic projection neurons within the GPe project to the SNr and also form part of a reciprocal connection with the subthalamic nucleus (STN) in which the GPe contributes GABAergic innervation of STN, while STN sends glutamatergic afferents to GPe. The influence of these pathways on cortical function ultimately arises via GABAergic SNr projections to thalamus that gate thalamocortical glutamatergic inputs (Figure 1).
