Hippocampal CA2 ripples recruit social replay and promote social memory

Abstract

The consolidation of spatial memory depends on the reactivation ('replay') of hippocampal place cells that were active during recent behavior. These reactivations are observed during sharp wave-ripples (SWRs), synchronous oscillatory events that occur during slow-wave sleep 1-9 and whose disruption impairs spatial memory consolidation 4,6,7,9 .Although the hippocampus encodes a wide range of non-spatial forms of declarative memory, it is not yet known whether SWRs are necessary for non-spatial memory.Moreover, although SWRs can arise from either the hippocampal CA3 8 or CA2 10 regions, the relative importance of these sources for memory consolidation is unknown. Here we examined the role of SWRs during the consolidation of social memory, the ability of an animal to recognize and remember a conspecific, focusing on CA2 because of its critical role in social memory 11,12,13 . We found that ensembles of CA2 pyramidal neurons that were active during social exploration of novel conspecifics were reactivated during SWRs. Importantly, disruption or enhancement of CA2 SWRs suppressed or prolonged social memory, respectively. Thus, SWR reactivation of hippocampal firing related to recent experience appears to be a general mechanism for binding spatial, temporal and sensory information into high-order memory representations.We employed a social recognition task that assessed social memory formation in mice without interference from other social behaviors. In this task, a subject mouse was first habituated to a square arena with two empty wire cup cages in opposite corners. Immediately after habituation, we placed a novel stimulus mouse in each of the empty cups (mouse S 1 and S 2 ). In social learning trial 1 the subject mouse was allowed to explore the arena for 5 min. This was immediately followed by a second 5 min social learning trial with the positions of the same Figure 1: Encoding of conspecifics by CA2 pyramidal cells activity. a) Schema of the task. b) Task performance in wild-type mice (n = 13). Social memory quantified during recall trial by a discrimination index (see Methods).

How development sculpts hippocampal circuits and function

“…It is now well established that the hippocampus also encodes non-spatial features (eg. time, odors, sound frequencies, conspecifics) (15,148,168) and ripples may therefore reactivate content other than spatial information (18).…”

The Neural Circuit Architecture of Social Hierarchy in Rodents and Primates

“…Indeed, CA2 inactivation produces striking deficits in social memory in a transgenic mouse model (Hitti and Siegelbaum, 2014 ). Since this publication, CA2 was found to contain a high proportion of social-sensitive cells and CA2 inactivation during social tasks inhibited the formation of social memories (Azahara et al, 2020 ). As CA2 has restricted output regions (Cui et al, 2013 ), ventral CA1 (vCA1) has been hypothesized as an intermediate region supporting most of the CA2 communication with cortical and subcortical targets (Meira et al, 2018 ).…”