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

Cell Rep. 2023 Jun 27;42(6):112662. doi: 10.1016/j.celrep.2023.112662. Epub 2023 Jun 20.

Abstract

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.

Keywords: CP: Neuroscience; KIBRA; anterior cingulate cortex; hippocampus; place cell; plasticity; sharp-wave ripple; sleep spindle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hippocampus* / physiology
  • Memory Consolidation* / physiology
  • Mice
  • Sleep / physiology

Substances

  • Wwc1 protein, mouse