AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP ?8 interactions

Abstract AMPA receptor (AMPAR) abundance and positioning at excitatory synapses regulates the strength of transmission. Changes in AMPAR localisation can enact synaptic plasticity, allowing long-term information storage, is therefore tightly controlled. Multiple mechanisms regulating anchoring have been described, but with limited coherence or comparison between reports, our understanding this process unclear. Here, combining recordings from mouse hippocampal slices super-resolution imaging dissociated cultures, we compare contributions three interaction domains controlling transmission CA1 synapses. We show that C-termini play only a modulatory role, whereas extracellular N-terminal domain (NTD) PDZ interactions auxiliary subunit TARP ?8 are both crucial, each sufficient to maintain Our data support model which accumulates AMPARs postsynaptic density, where NTD further tunes their positioning. This interplay cytosolic (TARP ?8) cleft provides versatility regulate plasticity.