PhD Rotation Project (2016-2017)

Functional role of divergent hippocampal CA2 circuits in social behaviors

@Columbia University

CA2 outputs mediate social behaviors (Siegelbaum Lab)

The CA2 subregion of the hippocampus had previously been neglected due to difficulties in manipulating the small region and physiological similarities to its more prominent neighboring CA1 and CA3 subregions. Through targeted ablations, Dr. Steve Siegelbaum's lab previously identified that CA2 is critical for the formation of social memories. During my rotation, we used viral techniques and identified two unique pathways: 1) a classical CA2 projection to CA1 and 2) a previously unidentified extrahippocampal projection to the lateral septum (LS). We pursued this novel projection to the ventromedial hypothalamus, a region known to regulate global aggression. To study the functional role of the CA2→CA1 and CA2→LS pathways, I developed social memory and social aggression assays in a traditionally slice physiology lab. By combining behavior with reversible chemogenetic inactivation (DREADD), we revealed that CA2→CA1 pathway is essential for forming social memory while CA2→LS circuit uniquely inhibits social aggression. My behavioral assays have become permanent mainstays in the lab, and my protocols continue to be used by new lab members.

Leroy, F., Park, J., Asok, A., Brann, D.H., Meira, T., Boyle, L.M., Buss, E.W., Kandel, E.R., & Siegelbaum, S.A. (2018). A circuit from hippocampal CA2 to lateral septum disinhibits social aggression. Nature.

Meira, T., Leroy, F., Buss, E.W., Oliva, A., Park, J., & Siegelbaum, S.A. (2018). A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics. Nature Communications.

Funding:

Ruth L. Kirschstein NRSA Institutional Training Grant (T32), 2016-2018 – National Institutes of Health