A circuit from the basolateral amygdala to hippocampal CA3 regulates social behavior.

Abstract

The CA3 region of the hippocampus is essential for associative memory. CA3 pyramidal neurons receive three canonical excitatory inputs-recurrent collaterals from other CA3 pyramidal neurons, mossy fiber input from the dentate gyrus (DG), and perforant path input from the entorhinal cortex-that terminate at specific dendritic compartments and have distinct functions. Yet, the additional extrahippocampal inputs to CA3 are less clear. Here, we report a monosynaptic glutamatergic input from the basolateral amygdala (BLA) that preferentially innervates ventral CA3. The CA3-projecting BLA neurons are topographically clustered in a small area near the medial border of BLA and preferentially innervate basal dendrites of distal CA3 (near CA1). Moreover, the BLA input preferentially excites regular-spiking CA3 pyramidal neurons expressing thorny excrescences, largely avoids burst-firing CA3 neurons lacking thorny excrescences (athorny cells), and only weakly excites CA2 pyramidal neurons. Furthermore, chemogenetic or optogenetic manipulations of the BLA-CA3 pathway bidirectionally alter social behavior. Taken together, our findings demonstrate that the BLA input constitutes a major glutamatergic input that can robustly excite CA3 pyramidal neurons in a cell-type- and subregion-specific manner and regulate social behavior.