Recently, a plasticity of the slow IPSCs in response to GABAB and D2 receptor activation has been observed (Figures 3b, 4). For example, depolarization of the postsynaptic neurons to bring the membrane potential close to 0 mV, increases the GABAB receptor-mediated IPSC several fold for the duration of the experiment129. This increased IPSC is independent of the activation of GABAB receptors, but dependent on NMDAR activation, similar to hippocampal NMDAR-dependent LTP of AMPAR-mediated EPSCs. It has been suggested that GIRK currents become larger because additional channels are inserted130. Indeed, the activation of NMDA receptor in cultured dissociated hippocampal neurons increases the level of the surface expression of GIRK1 and GIRK2 channel in the soma and dendrites within minutes130. This insertion requires protein phosphatase-1-mediated dephosphorylation of a GIRK2 serine residue (Ser-9) that promotes channel recycling. Increased expression of GIRK channels would reduce excitability, dampening signaling of hippocampal pyramidal neurons. For example, GIRK channel activation is implicated in the maintenance of LTP at glutamatergic synapses. In mice lacking GIRK2, the depotentiation of LTP in hippocampal neurons is impaired because adenosine A1 receptor fail to activate of GIRK channels 131.
