De-palmitoylation by N-(tert-Butyl) hydroxylamine inhibits AMPAR-mediated synaptic transmission via affecting receptor distribution in postsynaptic densities.

Aims Palmitoylation of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPARs) subunits or their “scaffold” proteins produce opposite effects on AMPAR surface delivery. Considering AMPARs have long been identified as suitable drug targets for central nervous system (CNS) disorders, targeting palmitoylation signaling to regulate AMPAR function emerges as a novel therapeutic strategy. However, until now, much less is known about the effect of palmitoylation‐deficient state on AMPAR function. Herein, we set out to determine the effect of global de‐palmitoylation on AMPAR surface expression and its function, using a special chemical tool, N‐(tert‐Butyl) hydroxylamine (NtBuHA).