AMPA Receptor Auxiliary Subunit GSG1L Suppresses Short-Term Facilitation in Corticothalamic Synapses and Determines Seizure Susceptibility

SUMMARY The anterior thalamus (AT) is critical for memory formation, processing navigational information, and seizure initiation. However, the molecular mechanisms that regulate synaptic function of AT neurons remain largely unexplored. We report that AMPA receptor auxiliary subunit GSG1L controls short-term plasticity in AT 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, AT 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 AT.
Graphical Abstract
In Brief Kamalova et al. report the phenotypes of GSG1L KO mice. The synaptic function of AMPAR auxiliary subunit GSG1L in the anterior thalamus is input specific. GSG1L suppresses short-term facilitation and decreases AMPAR activity specifically in corticothalamic synapses, where stargazin is functionally absent. GSG1L KO mice exhibit hyperexcitability and seizure susceptibility.