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Abstract

The emergence of genetic tools has provided new means of mapping
functionality in central amygdala (CeA) neuron populations based on
their molecular profiles, response properties, and importantly,
connectivity patterns. While abundant evidence indicates that neuronal
signals arrive in the CeA eliciting both aversive and appetitive
behaviors, our understanding of the anatomy of the underlying long-range
CeA network remains fragmentary. In this study, we combine viral
tracings, electrophysiological, and optogenetic approaches to establish
in male mice, a wiring chart between the insula cortex (IC), a major
sensory input region of the lateral and capsular part of the CeA
(CeL/C), and four principal output streams of this nucleus. We found
that retrogradely labeled output neurons occupy discrete and likely
strategic locations in the CeL/C, and that they are disproportionally
controlled by the IC. We identified a direct line of connection between
the IC and the lateral hypothalamus (LH), which engages numerous
LH-projecting CeL/C cells whose activity can be strongly upregulated on
firing of IC neurons. In comparison, CeL/C neurons projecting to the bed
nucleus of the stria terminalis (BNST) are also frequently contacted by
incoming IC axons, but the strength of this connection is weak. Our
results provide a link between long-range inputs and outputs of the CeA
and pave the way to a better understanding of how internal, external,
and experience dependent information may impinge on action selection by
the CeA.