NMDA Receptor-dependent Long-term Potentiation of Slow Synaptic Inhibition in Hippocampus

Synaptic plasticity, the cellular correlate for learning and memory, involves a number of molecules that reside in the dendritic spine. For example, long-term potentiation (LTP) of the excitatory postsynaptic current (EPSC) is induced by postsynaptic NMDA receptor and Ca 2+ /calmodulin-dependent kinase II (CaMKII) activity. Intrigued by recent findings that dendritic spines also harbor the metabotropic GABA B receptor for the major inhibitory transmitter GABA, as well as its downstream effector the G protein-activated inwardly rectifying K + (GIRK) channel, we wondered whether pairing glutamate release with postsynaptic depolarization would affect the slow inhibitory postsynaptic current (sIPSC) mediated by GABA B receptors and GIRK channels. Remarkably, we found that the same signaling pathway for inducing LTP of the EPSC also potentiated the sIPSC. Moreover, in mice lacking Nova-2, which is targeted in paraneoplastic opsoclonus myoclonus ataxia (POMA) patients and binds RNAs for synaptic proteins, the hippocampal CA1 neurons exhibited no LTP of slow synaptic inhibition.