Role of Hippocampal CA2 Region in Triggering Sharp-Wave Ripples

•Synchronous activity in CA2 region precedes sharp-wave ripples (SPW-Rs).•Activity of deep CA2 pyramidal cells ramps up before SPW-R, then quickly drops•Superficial CA2 cells fire synchronously preceding CA3 and CA1 during SPW-Rs•CA2 cells contribute more strongly to WAKE SPW-Rs while CA3 participates more in SLEEP

SummarySharp-wave ripples (SPW-Rs) in the hippocampus are implied in memory consolidation, as shown by observational and interventional experiments. However, the mechanism of their generation remains unclear. Using two-dimensional silicon probe arrays, we investigated the propagation of SPW-Rs across the hippocampal CA1, CA2, and CA3 subregions. Synchronous activation of CA2 ensembles preceded SPW-R-related population activity in CA3 and CA1 regions. Deep CA2 neurons gradually increased their activity prior to ripples and were suppressed during the population bursts of CA3-CA1 neurons (ramping cells). Activity of superficial CA2 cells preceded the activity surge in CA3-CA1 (phasic cells). The trigger role of the CA2 region in SPW-R was more pronounced during waking than sleeping. These results point to the CA2 region as an initiation zone for SPW-Rs.