Experience alters hippocampal and cortical network communication via a KIBRA-dependent mechanism

Synaptic plasticity is hypothesized to underlie "replay" of salient experience during hippocampal sharp-wave/ripple (SWR)-based ensemble activity and to facilitate systems-level memory consolidation coordinated by SWRs and cortical sleep spindles. It remains unclear how molecular changes at synapses contribute to experience-induced modification of network function. The synaptic protein KIBRA regulates plasticity and memory. To determine the impact of KIBRA-regulated plasticity on circuit dynamics, we recorded in vivo neural activity from wild-type (WT) mice and littermates lacking KIBRA and examined circuit function before, during, and after novel experience. In WT mice, experience altered population activity and oscillatory dynamics in a manner consistent with incorporation of new information content in replay and enhanced hippocampal-cortical communication. While baseline SWR features were normal in KIBRA conditional knockout (cKO) mice, experience-dependent alterations in SWRs were absent. Furthermore, intra-hippocampal and hippocampal-cortical communication during SWRs was disrupted following KIBRA deletion. These results indicate molecular mechanisms that underlie network-level adaptations to experience.