Quantitative Multiplex Immunoprecipitation (QMI) analysis of protein interaction network rearrangements during homeostatic plasticity

Neurons maintain constant levels of excitability using homeostatic synaptic scaling, which adjusts the strength of all of a neuron’s postsynaptic inputs to compensate for large changes in overall activity. Here, we asked how prolonged changes in activity affect network-level protein interactions at the synapse. We assessed a glutamatergic synapse protein interaction network (PIN) composed of 380 binary associations among 21 protein members to identify protein complexes altered by activity manipulation in vitro or sensory deprivation in vivo. In cultured cortical neurons, we observed widespread bidirectional PIN alterations during up- and downscaling that reflected rapid rearrangements of glutamate receptor co-associations via synaptic scaffold remodeling. Sensory deprivation of the barrel cortex caused unique PIN rearrangements, including changes in co-associations between the glutamate receptor mGluR5 and the kinase Fyn, consistent with emerging models of experience dependent plasticit...