The amygdala is critical for the expression and learning of fear responses. Although much is known about the functions of the amygdala, how it works remains obscure, in part because we do not understand its intrinsic network. Given the implication of the amygdala in fear, it is likely that we could improve our understanding of human anxiety disorders by performing basic research on the amygdala. Thus, I propose to characterize the intrinsic circuit of the amygdala, using in vitro and in vivo electrophysiological methods, as well as single-cell labeling and immunohistochemistry at the light and electron microscopic (EM) level. As a first step, this project will focus on the lateral amygdaloid nucleus (LA) because it is the main input station of the amygdala for sensory afferents. ? ? The cellular composition of the LA is similar to that of the cortex in terms of physiological properties and neurotransmitters. Yet, compared to cortical cells, LA projection cells (P-cells) have extremely low firing rates. This is puzzling because the LA is endowed with a massive system of excitatory intrinsic projections. Inhibition thus emerges as a key determinant of LA activity. This is why the present project focuses on feedback inhibition in the LA. It is hypothesized that feedback interneurons effectively divide the LA nucleus in transverse processing modules. Specifically, P-cells would contact different cell types depending on rostrocaudal distance to target: in the same coronal plane, P-cells would prevalently contact feedback interneurons; at more distant sites in the rostrocaudal axis, they would mainly contact other P-cells. This architecture would allow intermixing of sensory information in the rostrocaudal plane while preventing runaway excitation within each module. ? ? Taking advantage of the strong projection from the LA to the basomedial (BM) amygdala, this hypothesis will be tested by comparing the responses of LA P-cells and feedback interneurons to BM stimuli in horizontal vs. coronal amygdala slices kept in vitro. We will also determine whether P-cells contact different cell types depending on rostrocaudal distance to target. To this end, P-cells will be filled with neurobiotin during intracellular recordings in vivo and their axons will be examined in the EM.
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