Date: October 28, 2016. 12:00
Location: CCU Seminar Room
Affiliation: Emory University, Georgia, United States.
Neurons have a complex morphology, with branched dendrites exhibiting thousands of synapses. We are interested in understanding how these connections between nerve cells are modified with experience. The ability of synapses to change their strength is thought to be the cellular correlate of learning and memory, and synaptic dysfunction is present in neuropsychiatric disorders.
N-methyl-D-aspartate receptors (NMDAR) play a central role in shaping the strength of synaptic connections throughout development and in mediating synaptic plasticity mechanisms. The contribution of each subunit to the synaptic traffic of NMDAR is still controversial. We find a critical role for the GluN2B subunit in regulating NMDAR synaptic targeting, and the synaptic level of ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) receptors; GluN2B-mediated anchoring of the synaptic proteasome is responsible for fine tuning AMPAR synaptic levels under basal conditions.
Neurons are constantly refining their connections in response to changes in activity. Experience-dependent plasticity is a key form of synaptic plasticity, involving changes in AMPAR accumulation at synapses. The AMPAR auxiliary subunit stargazin is crucial for this plasticity. Stargazin phosphorylation is essential for homeostatic synaptic scaling, and in the absence of stargazin, the refinement of the retinogeniculate synapse is specifically disrupted during the experience-dependent phase. Our data reveal an important role for stargazin in regulating AMPAR abundance at glutamatergic synapses during homeostatic and experience-dependent plasticity. Interestingly, disease-associated mutations in stargazin disrupt its role in homeostatic plasticity.