Hunger States Control the Directions of Synaptic Plasticity via Switching Cell Type-Specific Subunits of NMDA Receptors
Hunger States Control the Directions of Synaptic Plasticity via Switching Cell Type-Specific Subunits of NMDA Receptors
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DOI：
10.1523/jneurosci.0855-15.2015
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发表时间：
2015-09-23
影响因子：
5.3
通讯作者：
Yang, Yunlei
中科院分区：
文献类型：
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作者：
Qi, Yong;Yang, Yunlei
饥饿状态是否以及如何控制活动依赖性突触可塑性，如长时程增强（LTP）和长时程抑制（LTD），在很大程度上仍然未知。我们在这里报告的LTP和LTD的兴奋性突触强度的食欲控制回路驻留在下丘脑弓状核（ARC）的行为方式的饥饿状态依赖性和细胞类型特异性。例如，我们发现，强直刺激诱导LTP在食欲agouti-related蛋白（AgRP）神经元在随意喂养的小鼠，而它诱导LTD在食物剥夺的小鼠。在相反的方向，相同的诱导方案诱导LTD在approxigenic阿黑皮素（POMC）神经元喂养的小鼠，但弱LTP剥夺小鼠。从机制上讲，我们还发现，食物剥夺增加的表达NR 2C/NR 2D/NR 3-含有NMDA受体（NMDARs）的AgRP神经元，有助于LTD的诱导，而它减少其在POMC神经元的表达。总的来说，我们的数据显示，饥饿状态控制的方向，通过切换NMDA受体亚群在细胞类型特异性的方式，能量状态和联想记忆之间的NMDAR介导的相互作用的活动依赖性突触可塑性。
It remains largely unknown whether and how hunger states control activity-dependent synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). We here 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 switching NMDA receptor subpopulations in a cell type-specific manner, providing insights into NMDAR-mediated interactions between energy states and associative memory.