Description:

The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents:

Jeffrey N. Savas, PhD
Assistant Professor of Neurology (Behavioral Neurology), Medicine and Pharmacology
Northwestern University Feinberg School of Medicine

Activity-induced proteome remodeling is important for synapse strengthening, however a comprehensive understanding of the protein networks and pathways responsible for this key neurobiological process have been unknown. Here, we performed transcriptomic and proteomic analyses and identified extracellular vesicles (EVs) as critical regulators of the early molecular events underlying NMDAR-dependent synaptic strengthening. Rapidly after NMDAR activation, the key EV proteins Alix and Tsg101 are synthesized, localize to synapses, and promote EV release from neurons. To our surprise, synaptic activity-induced EVs lack Arc protein but contained abundant levels of phosphorylated CaMKII and additional synaptic proteins. EVs can be taken up by nearby neurons and induce bi-directional synaptic signaling via subsequent phosphorylation of CaMKII in unstimulated neurons. Blocking ceramide production, which is required for EV biogenesis, inhibited the enhancement of mEPSC amplitudes after glycine treatment. Taken together with recent findings neuronal EVs play previously underappreciated and diverse roles in regulating synaptic strength.