Hippocampal CA2 Organizes CA1 Slow and Fast γ Oscillations during Novel Social and Object Interaction.

ABSTRACT

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 γ 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; Lasztóczi and Klausberger, 2014, 2016) reflective of its inputs (Fernández-Ruiz et al., 2012; Schomburg et al., 2014), and because CA2 activity controls CA1 slow γ (Alexander et al., 2018), we hypothesized that silencing CA2 would affect CA1 slow γ 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 γ power during investigation of a novel animal and fast γ 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 γ oscillations in a stimulus-specific manner.