Genetic and experimental evidence supports the continuum of the central extended amygdala and a mutiple embryonic origin of its principal neurons

Abstract

The central extended amygdala is the major output center for telencephalic control of ingestion, fear responses, stress, and anxiety. In spite of the abundant data supporting the similarity in neurochemistry, connections, and function along the extended amygdala, embryological support for this continuum is lacking. By using a combination of in vitro migration assays, in situ hybridization, and immunostaining, here we show that its major components, including central amygdala and lateral bed nucleus of the stria terminalis (BST), are mosaics formed by different proportions of dorsal lateral ganglionic eminence (LGE)-, ventral LGE-, and medial ganglionic eminence (MGE)-derived principal neurons. The dorsal LGE produces Pax6-expressing neurons that primarily populate lateral parts of the central extended amygdala, including the capsular and part of lateral central amygdala, but also produces a few cells for the lateral BST. Based on correlation with preproenkephalin, many of these cells are likely enkephalinergic. The ventral LGE produces Islet1-expressing neurons that populate primarily the central and medial parts of the central amygdala but also produces numerous neurons for the lateral BST. Correlation with corticotropin-releasing factor suggests that these neurons express this neuropeptide. The MGE produces the majority of neurons of the lateral BST, but its ventrocaudal subdivision also produces an important subpopulation of projection neurons containing somatostatin for medial aspects of the central amygdala. Thus, distinct principal neurons originate in different embryonic domains, but the same domains contribute neurons to most subdivisions of the central extended amygdala, which may explain the similarity in neurochemistry and connections along the corridor.