University of California, San Francisco (UCSF)

Shuffling AMPA Receptors: TARPs and Synaptic Plasticity

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Excitatory synaptic transmission occurs when presynaptic glutamate is released and activates postsynaptic AMPA receptors. Synaptic plasticity, or the fine-tuning in the strength of synaptic transmission that underlies such phenomena as learning and memory, occurs when AMPA receptors are shuttled into and out of the postsynaptic membrane. A family of four proteins (gamma-2, gamma-3, gamma-4, and gamma-8), called transmembrane AMPA receptor regulatory proteins (TARPs), facilitate AMPA receptor trafficking, and one family member, gamma-2, is required for membrane expression of functional AMPA receptors in cerebellar granule cells. Deletion of gamma-2 alone is not sufficient to eliminate AMPA receptor activity or synaptic plasticity in other other neurons, consistent with the expression of additional TARP family members in these areas. By eliminating all TARPs, I propose to demonstrate a requirement for these proteins for functional AMPA receptor expression throughout the brain, using electrophysiological investigations of genetically-modified mice. These studies, which will focus initially on the hippocampus (an area critical for learning and memory), may also yield insight into the specific roles of individual TARP family members.