TY - JOUR T1 - Hippocampal CA2 Organizes CA1 Slow and Fast Gamma Oscillations during Novel Social and Object Interaction JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0084-20.2020 SP - ENEURO.0084-20.2020 AU - Logan Y. Brown AU - Georgia M. Alexander AU - Jesse Cushman AU - S.M. Dudek Y1 - 2020/03/13 UR - http://www.eneuro.org/content/early/2020/03/13/ENEURO.0084-20.2020.abstract N2 - A key goal in hippocampal research is to understand how neuronal activity is generated and organized across hippocampal subregions to enable memory formation and retrieval. Neuronal activity in CA2 is regulated by spatial and social investigation as well as by novelty (Mankin et al., 2015; Alexander et al., 2016), and CA2 activity controls population oscillatory activity in the slow gamma and ripple ranges within hippocampus (Kay et al., 2016; Oliva et al., 2016; Boehringer et al., 2017; Alexander et al., 2018). CA2 neurons are also required for social recognition memory (Stevenson and Caldwell, 2012; Hitti and Siegelbaum, 2014; Smith et al., 2016). Because CA1 exhibits layer-specific organization (Scheffer-Teixeira et al., 2012; Lasztoczi and Klausberger, 2014, 2016) reflective of its inputs (Fernandez-Ruiz et al., 2012; Schomburg et al., 2014), and because CA2 activity controls CA1 slow gamma (Alexander et al., 2018), we hypothesized that silencing CA2 would affect CA1 slow gamma in a layer-specific manner during investigation of a novel social stimulus. While recording from CA1, we leveraged molecular tools to selectively target and inhibit CA2 pyramidal cells using inhibitory DREADDs while subject mice investigated novel animals or objects. We found that CA2 inhibition reduced slow gamma power during investigation of a novel animal and fast gamma power during both novel object and animal investigation in a manner reflective of the CA2 axonal projection zones within CA1. Our results suggest that CA2 contributes to CA1 slow and fast gamma oscillations in a stimulus-specific manner.SIGNIFICANCE STATEMENT Using chemogenetics and electrophysiology, we show that CA2 contributes to slow gamma oscillations in CA1 during novel animal investigation and fast gamma during novel animal or object investigation in a layer-specific manner reflective of CA2 connectivity. Slow gamma oscillations in CA1 rely on CA3 and CA2 input during running, and CA2 neuronal activity is required for social memory. Our findings of reduced slow gamma oscillations in CA1 layers targeted by CA2 axons upon reduction of CA2 activity support the involvement of CA2 in slow gamma oscillations, and the finding that slow gamma oscillations were impaired by CA2 silencing selectively during novel animal investigation are consistent with a role for CA2 in social cognition. ER -