Functional Characterization of an AMPA receptor auxiliary subunit GSG1L in vivo

Abstract

AMPA receptors (AMPAR) are key mediators of fast excitatory neurotransmission within the brain. The functional identity of AMPAR at the synapses strongly contributes to molecular mechanisms of learning and memory. At the synapse, AMPARs are bound to their auxiliary subunits, which have a profound effect on AMPAR biogenesis. GSG1L is a recently identified auxiliary subunit that has a strong AMPAR regulatory function, unlike any known auxiliary subunit. The work presented in this dissertation aimed to determine the postsynaptic function of GSG1L. We report that AMPA receptor auxiliary subunit GSG1L controls short-term plasticity in anterior thalamic synapses that receive inputs from the cortex, but not in those receiving inputs from other pathways. A canonical auxiliary subunit stargazin co-exists in these neurons but is functionally absent from corticothalamic synapses. In GSG1L knockout mice, anterior thalamic neurons exhibit hyperexcitability and the animals have increased susceptibility to seizures, consistent with a negative regulatory role of GSG1L. We hypothesize that negative regulation of synaptic function by GSG1L plays a critical role in maintaining optimal excitation in the anterior thalamus.