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Siegelbaum, S. A.

Publications and source records attributed to Siegelbaum, S. A..

2 recordsLinked to original sources

Hippocampal CA2 ripples recruit social replay and promote social memory

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 sleep1-9 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 CA38 or CA210 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 memory11,12,13. 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.

neuroscience

Coding of social novelty in the hippocampal CA2 region and its disruption and rescue in a mouse model of schizophrenia

The hippocampal CA2 region is essential for social memory and has been implicated in neuropsychiatric disorders. However, little is known about how CA2 neural activity encodes social interactions and how this coding is altered in disease. We recorded from CA2 pyramidal neurons as mice engaged in social interactions and found that while CA2 failed to stably represent spatial location, CA2 activity encoded contextual changes and novel social stimuli. In the Df(16)A+/- mouse model of the human 22q11.2 microdeletion, a major schizophrenia risk factor, CA2 activity showed a surprising increase in spatial coding while failing to encode social novelty, consistent with the social memory deficit in these mice. Previous work has shown that CA2 pyramidal neurons are hyperpolarized in Df(16)A+/- mice, likely as a result of upregulation of TREK-1 K+ current. We found that administration of a TREK-1 antagonist rescued the social memory deficits and restored normal CA2 coding properties in Df(16)A+/- mice, supporting a crucial role for CA2 in the encoding of novel social stimuli and social dysfunction.

neuroscience