Contribution of genoarchitecture to understanding forebrain evolution and development, with particular emphasis on...

The amygdala is a forebrain center involved in functions and behaviors that are critical for survival (such as control of the neuroendocrine system and homeostasis, and reproduction and fear/escape responses) and in cognitive functions such as attention and emotional learning. In mammals, the amygdala is highly complex, with multiple subdivisions, neuronal subtypes, and connections, making it very difficult to understand its functional organization and evolutionary origin. Since evolution is the consequence of changes that occurred in development, herein we review developmental data based on genoarchitecture and fate mapping in mammals (in the mouse model) and other vertebrates in order to identify its basic components and embryonic origin in different species and understand how they changed in evolution. In all tetrapods studied, the amygdala includes at least 4 components: (1) a ventral pallial part, characterized by expression of Lhx2 and Lhx9, that includes part of the basal amygdalar complex in mammals and a caudal part of the dorsal ventricular ridge in sauropsids and also produces a cell subpopulation of the medial amygdala; (2) a striatal part, characterized by expression of Pax6 and/or Islet1, which includes the central amygdala in different species; (3) a pallidal part, characterized by expression of Nkx2.1 and, in amniotes, Lhx6, which includes part of the medial amygdala, and (4) a hypothalamic part (derived from the supraoptoparaventricular domain or SPV), characterized by Otp and/or Lhx5 expression, which produces an important subpopulation of cells of the medial extended amygdala (medial amygdala and/or medial bed nucleus of the stria terminalis). Importantly, the size of the SPV domain increases upon reduction or lack of Nkx2.1 function in the hypothalamus. It appears that Nkx2.1 expression was downregulated in the alar hypothalamus during evolution to mammals, which may have produced an enlargement of SPV and the amygdalar cell subpopulation derived from it.