Therefore, we propose a working model (Supplementary Fig. 12), in which postsynaptic ASIC1a regulates insular LTD induction through Ca2+-induced activation of phosphatase 1/2A and then GSK3β, either dependent or independent of NMDAR, which ultimately drives AMPAR internalization56 to cause synaptic depression. The gene discussed is GSK3B; the disease is depressive disorder.