Cell-type specific parallel circuits in the bed nucleus of the stria terminalis and the central nucleus of the amygdala of the mouse

Abstract

The central extended amygdala (EAc) is a forebrain macrosystem which has been widely implicated in reward, fear, anxiety, and pain. Its two key structures, the lateral bed nucleus of the stria terminalis (BSTL) and the central nucleus of the amygdala (CeA), share similar mesoscale connectivity. However, it is not known whether they also share similar cell-specific neuronal circuits. We addressed this question using tract-tracing and immunofluorescence to reveal the EAc microcircuits involving two neuronal populations expressing either protein kinase C delta (PKCδ) or somatostatin (SOM). PKCδ and SOM are expressed predominantly in the dorsal BSTL (BSTLD) and in the lateral/capsular parts of CeA (CeL/C). We found that, in both BSTLD and CeL/C, PKCδ+ cells are the main recipient of extra-EAc inputs from the lateral parabrachial nucleus (LPB), while SOM+ cells constitute the main source of long-range projections to extra-EAc targets, including LPB and periaqueductal gray. PKCδ+ cells can also integrate inputs from the basolateral nucleus of the amygdala or insular cortex. Within EAc, PKCδ+, but not SOM+ neurons, serve as the major source of inputs to the ventral BSTL and to the medial part of CeA. However, both cell types can be involved in mutual connections between BSTLD and CeL/C. These results unveil the pivotal positions of PKCδ+ and SOM+ neurons in organizing parallel cell-specific neuronal circuits within CeA and BSTL, but also between them, which further reinforce the notion of EAc as a structural and functional macrosystem.

Keywords: Central extended amygdala; Microcircuit; Neuronal tracing; Protein kinase C delta type; Somatostatin.