Hippocampal place code plasticity in CA1 requires postsynaptic membrane fusion

Abstract

SummaryRapid delivery of glutamate receptors to the postsynaptic membrane via vesicle fusion is a central component of synaptic plasticity. However, it is unknown how this process supports specific neural computations during behavior. To bridge this gap, we combined conditional genetic deletion of a component of the postsynaptic membrane fusion machinery, Syntaxin3 (Stx3), in hippocampal CA1 neurons of mice with populationin vivocalcium imaging. This approach revealed that Stx3 is necessary for forming the neural dynamics that support novelty processing, spatial reward memory and offline memory consolidation. In contrast, CA1 Stx3 was dispensable for maintaining aspects of the neural code that exist presynaptic to CA1 such as representations of context and space. Thus, manipulating postsynaptic membrane fusion identified computations that specifically require synaptic restructuring via membrane trafficking in CA1 and distinguished them from neural representation that could be inherited from upstream brain regions or learned through other mechanisms.

Reward Expectation Reduces Representational Drift in the Hippocampus

“…Therefore, reduction of dopamine released in the hippocampus from the VTA with lowered reward expectation likely contributes to the observed reduction in lap-to-lap reliability and subsequent instability of place fields across days. Dopamine may accomplish this by enhancing the plasticity mechanisms that drive the reliability and stability of salient memories (Bittner et al, 2017;Madar et al, 2023;Plitt & Giocomo, 2021;Plitt et al, 2023;Thomas et al, 2023). Dopamine release during periods of heightened reward expectation may indirectly enhance the stability of place maps by strengthening functional network correlations in CA1.…”