Multiple telencephalic and extratelencephalic embryonic domains contribute neurons to the medial extended amygdala

Abstract

Dysfunctions in emotional control and social behavior are behind human neuropsychiatric disorders, some of which are associated with an alteration of amygdalar development. The medial extended amygdala is a key telencephalic center for control of social behavior, but very little is known about its development. We used in vitro migration assays for analyzing the origin of the neurons of the medial extended amygdala in mouse embryos (E13.5–E16.5). We compared the migration assays with immunofluorescence/immunohistochemistry for calbindin and radial glial fibers and with mRNA expression of several genetic markers of distinct forebrain subdivisions. We provide experimental evidence for multiple embryonic origins of the principal neurons of the medial extended amygdala. In particular, we provide novel evidence indicating that a major part of the neurons derives from a caudoventral pallidal subdivision (previously called or included as part of the anterior peduncular area), forming a cell corridor with similar molecular features (expression of Lhx6 and calbindin), connectivity, and function, which relates to reproductive behavior. We also provide novel experimental evidence indicating that the ventral pallium produces some neurons for the medial amygdala, which correlates with data from Lhx9 expression. Our results also confirm that some neurons of the medial extended amygdala originate in the preoptic area (our results indicate that these cells specifically originate in its commissural subdivision) and the supraoptoparaventricular domain of the hypothalamus. Our study helps to set up the foundations for a better understanding of medial amygdalar control of behavior in normal and abnormal conditions.