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

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.