Local Guanethidine for Proptosis

Abstract

<h3>Abstract</h3> 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. However, it remains unclear how molecular changes at synapses contribute to experience-induced modification of network function. The synaptic protein KIBRA regulates plasticity and memory, although its impact on circuit dynamics remains unknown. Here, we recorded <i>in vivo</i> neural activity from WT mice and littermates lacking KIBRA to examine circuit function before, during, and after novel experience. In WT mice, experience altered network dynamics in a manner consistent with incorporation of new information content in replay and enhanced hippocampal-cortical communication. However, while baseline SWR features were normal in KIBRA 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 reveal molecular mechanisms that underlie network-level memory formation and consolidation.