Synapse type-specific multi-omics mapping of sensory experience-induced plasticity

 Synaptic plasticity remains a difficult process to study in detail, because its manifestation highly varies and is dependent on many factors, including the type of synapse. It has therefore proven to be challenging to apply unbiased screens to these specific neuronal compartments in a physiologically relevant manner. As a result, molecular mechanisms of synaptic plasticity remain poorly characterized. Our lab has recently developed a method to specifically isolate mossy fiber (MF) synaptosomes based on biochemical enrichment and fluorescence activated sorting. This provides a unique opportunity to study the molecular mechanisms underlying synaptic plasticity of a specific synapse type. MF synapses are key players in the information processing pathway of the hippocampus and undergo marked structural and functional changes when stimulated by environmental enrichment. I hypothesize that the increased morphological complexity upon environmental enrichment will be reflected in changes in the molecular composition of MF synapses, revealing novel molecular mechanisms important for synaptic plasticity. The goal of the experiments proposed here is to map the molecular changes in MF synapses upon sensory experience and identify key players that regulate synaptic plasticity. By characterizing the effect of loss-offunction of these candidate proteins, I aim to identify novel molecular mechanisms that regulate structural and functional plasticity.