UC San Diego

The hippocampus plays a fundamental role in the immediate processing of afferent information from many brain regions and has been linked to emotional regulation, learning and memory formation, and spatial processing. Decoded neuronal activity during sharp-wave ripple (SWR) events has shown how hippocampal place cells are activated during SWRs, and these place cells code for future goal locations. Additionally, these future goal locations on complex spatial WM tasks are no longer represented during SWR events when the dentate gyrus (DG) is lesioned, leading us to hypothesize that SWR events generated in the CA3 region of the hippocampus are necessary for guiding ongoing spatial working memory (WM) behavior. We analyzed the real-time local field potential (LFP) for SWRs while animals performed a complex spatial WM task, and we electrically stimulated the ventral hippocampal commissural fibers to induce transient silencing of pyramidal neurons in CA1 and CA3 to prevent place cell reactivation during SWR events. Disruption of CA3 SWRs did not cause any significant spatial WM performance deficits compared to controls, suggesting that CA3 SWRs are not causally linked to spatial WM processes. Therefore, contrary to this popular belief in the field, our results indicate SWR events are not the primary mechanism for guiding hippocampal-dependent spatial WM behavior.