The expanded circuitry of hippocampal ripples and replay.

The place cells and well-defined oscillatory population rhythms of the rodent hippocampus have served as a powerful model system in linking cells and circuits to memory function. While the initial three decades of place cell research primarily focused on the activity of neurons during exploration, the last twenty-five years have seen growing interest in the physiology of the hippocampus at rest. During slow-wave sleep and quiet wakefulness the hippocampus exhibits sharp-wave ripples (SWRs), short high-frequency, high-amplitude oscillations, that organize the reactivation or 'replay' of sequences of place cells, and interventions that disrupt SWRs impair learning. While the canonical model of SWRs generation have emphasized CA3 input to CA1 as the source of excitatory drive, recent work suggests there are multiple circuits, including the CA2 region, that can both influence, generate and organize SWRs, both from the oscillatory and information content perspectives in a task and state-dependent manner. This extended circuitry and its function must be considered for a true understanding of the role of the hippocampus in off-line processes such as planning and consolidation.

Lateralization of CA1 assemblies in the absence of CA3 input.

In the hippocampal circuit CA3 input plays a critical role in the organization of CA1 population activity, both during learning and sleep. While integrated spatial representations have been observed across the two hemispheres of CA1, these regions lack direct connectivity and thus the circuitry responsible remains largely unexplored. Here we investigate the role of CA3 in organizing bilateral CA1 activity by blocking synaptic transmission at CA3 terminals through the inducible transgenic expression of tetanus toxin. Although the properties of single place cells in CA1 were comparable bilaterally, we find a decrease of ripple synchronization between left and right CA1 after silencing CA3. Further, during both exploration and rest, CA1 neuronal ensemble activity is less coordinated across hemispheres. This included degradation of the replay of previously explored spatial paths in CA1 during rest, consistent with the idea that CA3 bilateral projections integrate activity between left and right hemispheres and orchestrate bilateral hippocampal coding.