LAUSR

HighlightsUsed biophysical models of hippocampal sleep SWR activity to study memory reactivation.Reactivation in CA3 requires fine tuning of excitatory and inhibitory synapses.Excitatory pathways from CA3 to CA1 specifically shape sequence reactivation in CA1.CA1 activity can exert a form of dynamic gating over CA3 sharp wave activity.Hippocampal awake learning needs to coordinate with reactivation in previous sleep. Abstract The hippocampus is important for memory and learning, being a brain site where initial memories are formed and where sharp wave – ripples (SWR) are found, which are responsible for mapping recent memories to long‐term storage during sleep‐related memory replay. While this conceptual schema is well established, specific intrinsic and network‐level mechanisms driving spatio‐temporal patterns of hippocampal activity during sleep, and specifically controlling off‐line memory reactivation are unknown. In this study, we discuss a model of hippocampal CA1‐CA3 network generating spontaneous characteristic SWR activity. Our study predicts the properties of CA3 input which are necessary for successful CA1 ripple generation and the role of synaptic interactions and intrinsic excitability in spike sequence replay during SWRs. Specifically, we found that excitatory synaptic connections promote reactivation in both CA3 and CA1, but the different dynamics of sharp waves in CA3 and ripples in CA1 result in a differential role for synaptic inhibition in modulating replay: promoting spike sequence specificity in CA3 but not in CA1 areas. Finally, we describe how awake learning of spatial trajectories leads to synaptic changes sufficient to drive hippocampal cells’ reactivation during sleep, as required for sleep‐related memory consolidation.