Dopaminergic innervation at the central nucleus of the amygdala reveals distinct topographically and functionally segregated regions

The central nucleus of the amygdala (CeA) is involved in the expression of fear and has been implicated in several anxiety disorders. Anatomically, it is divided in a medial (CeM), a lateral (CeL) and a capsular division (CeC). The CeA is densely innervated by dopaminergic projections that originate in the ventral periaqueductal gray/dorsal raphe (vPAG/DR) and the ventral tegmental area/substantia nigra compacta (VTA/SNc). However, it is unknown if DA exerts a homogenous control over the CeA or, conversely, if different parts of the CeA are regulated in a distinct manner. Here, we performed a neuroanatomical and functional analysis of the mouse CeA and revealed that dopaminergic innervations arriving from the PAG/DR and the VTA/SNc constitute distinct, non-overlapping pathways that differ in their expression of dopamine transporter. By quantifying the distribution of DAergic fibers and the origin of the innervation, we identified two regions in the CeL: a frontal region innervated by both the VTA/SNc and the vPAG/DR, and a caudal region innervated only by the vPAG/DR; and three regions in the CeC: a fronto-dorsal region innervated only by the VTA/SNc, a fronto-ventral region with sparse DAergic innervation, and a caudal region with low innervation from the vPAG/DR. In addition, we found that each region displays a unique pattern of cFos activation after the administration of cocaine, SKF 38393, quinpirole or haloperidol, demonstrating that the regions identified here are functionally distinct from each other. In summary, this analysis reveals unique properties of the DAergic pathways innervating the CeA, and distinguishes six topographically segregated and functionally distinct regions in the CeA. This unanticipated level of functional heterogeneity calls for more precise anatomical specificity in future functional studies of the CeA.