Molecular fingerprinting of potentiated synapses using an activity-dependent probe for proteomics

We created a pair of AAV-carried constructs to immunoprecipitate the interactome of the synaptic hub protein PSD95 specifically at potentiated synapses, or from the whole synaptic bulk. Either AAV was stereotaxically injected into the mouse hippocampus. Injected mice were exposed to contextual fear conditioning to trigger synaptic plasticity and potentiation. Immunoprecipitation was then performed and samples were processed for mass spectrometry. These data can be reused to implement computational models of the structural features differentiating a potentiated synapse from a basally active one, thus providing a molecular basis for memory at the synaptic scale.