Hunger states control the directions of synaptic plasticity via switching cell type-specific subunits of NMDA receptors

It remains largelyunknownwhether andhowhunger states control activity-dependent synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD).Wehere report that both LTP and LTD of excitatory synaptic strength within the appetite control circuits residing in hypothalamic arcuate nucleus (ARC) behave in a manner of hunger states dependence and cell type specificity. For instance, we find that tetanic stimulation induces LTP at orexigenic agouti-related protein (AgRP) neurons in ad libitum fed mice, whereas it induces LTD in food-deprived mice. In an opposite direction, the same induction protocol induces LTD at anorexigenic pro-opiomelanocortin (POMC) neurons in fed mice but weak LTP in deprived mice. Mechanistically, we also find that food deprivation increases the expressions of NR2C/NR2D/NR3-containing NMDA receptors (NMDARs) at AgRP neurons that contribute to the inductions of LTD, whereas it decreases their expressions at POMC neurons. Collectively, our data reveal that hunger states control the directions of activity-dependent synaptic plasticity by switchingNMDAreceptor subpopulations in a cell type-specific manner, providing insights into NMDAR-mediated interactions between energy states and associative memory.