Working model of the major circuitry change in the ChAT-p11 cKO mouse model of depression. (A) Summary of the major projections to the ChIs of the nucleus accumbens: ChIs of the nucleus accumbens receive large number of projections from multiple regions of the brain. The line width represents the proportion of cells in that brain region projecting to the nucleus accumbens, relative to other regions. dmPFC – dorsomedial prefrontal cortex; M – motor cortex; S – somatosensory cortex; Au & V – auditory and visual cortices; vHIP – ventral hippocampus; medTHA - medial thalamic nuclei; LH - lateral hypothalamus, AMY – amygdaloid nuclei; subTHA - subthalamic region; VTA – ventral tegmental area; DR - dorsal raphe; and Tg – tegmental area. (B) Schematic diagram of the changes in ChIs projections in the mouse model of depression: In the wild type mice accumbal ChIs receive glutamatergic projections from three areas, medial orbital PFC (purple), vHIP (teal), and central amygdaloid nucleus (maroon), that appear to be important for their tonic activity and non-depressive phenotype. In the mouse model of depression inputs from the ventral hippocampus are significantly reduced, and tonic activity of the ChIs is severely changed, resulting in a depressive phenotype.