A molecular signature of slow AMPA receptors
Andrew Plested
Professor of Cellular Biophysics – Humboldt University Berlin
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Résumé
At excitatory synapses, glutamate activates receptors in the postsynaptic membrane including the AMPA receptor. Usually considered to be the fastest receptor in the brain, AMPA receptors can produce millisecond synaptic potentials that mimic the timing of spikes. However, we found abundant slow AMPA responses in CA1 pyramidal cells with a mosaic distribution even in single dendrites (Pampaloni et al, 2021). To enable a detailed interrogation of these slow AMPA receptors, we sought to determine their molecular basis. Slow AMPA responses are prevalent in ventral CA1 but rather sparse in dorsal hippocampus, and absent in dentate gyrus granule cells. Some AMPA receptor components also show gradients across these hippocampal regions in published transcriptomic data. One such class of auxiliary protein, the Cornichon homologs, produces very slow AMPA responses in heterologous expression. Strikingly, we found that shRNA against Cornichon subunits largely ablated slow AMPA responses in ventral CA1, whereas over-expression in dorsal CA1 introduced slow AMPA responses. We conclude that Cornichon homologs are sparsely-expressed markers of slow AMPA currents that convert individual synapses into detonators that can spike the target cell, with implications for circuits and behaviour.

Invité par Rosa Cossart