Hippocampal place code plasticity in CA1 requires postsynaptic membrane fusion

Rapid 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 hippocampal CA1 deletion of the t-SNARE protein Syntaxin3 (Stx3), a component of the postsynaptic membrane fusion machinery, with population in vivo calcium imaging. This approach revealed that Stx3 is necessary for neural responses to novelty and for forming stable representations of rewarded locations. By contrast, CA1 Stx3 is dispensable for maintaining aspects of the neural code that exist presynaptic to CA1, such as representations of context and space. Thus, altering the Stx3-dependent postsynaptic membrane fusion machinery identified computations that specifically require synaptic restructuring via membrane trafficking in CA1 and distinguished them from neural representations that could be inherited from upstream brain regions or learned through other mechanisms.