Summary

Dynamic regulation of calcium-permeable (CP-) AMPARs is important in normal synaptic transmission, plasticity and pathological changes. While the involvement of TARPs in trafficking of calcium-impermeable (CI-) AMPARs has been extensively studied, their role in surface expression and function of CP-AMPARs remains unclear. Here we examined AMPAR-mediated currents in cerebellar stellate cells from stargazer mice, lacking the prototypical TARP stargazin (γ-2). We found a marked increase in the contribution of CP-AMPARs to synaptic responses, indicating that, unlike CI-AMPARs, these can localize at synapses in the absence of γ-2. In contrast with CP-AMPARs in extrasynaptic regions, synaptic CP-AMPARs displayed an unexpectedly low channel conductance and strong block by intracellular spermine, suggesting they were ‘TARPless’. As proof of principle that TARP-association is not an absolute requirement for AMPAR clustering at synapses, mEPSCs mediated by TARPless AMPARs were readily detected in stargazer granule cells following knock down of their only other TARP, γ-7