Hunger States Switch a Flip-Flop Memory Circuit via a Synaptic AMPK-Dependent Positive Feedback Loop
Hunger States Switch a Flip-Flop Memory Circuit via a Synaptic AMPK-Dependent Positive Feedback Loop
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DOI：
10.1016/j.cell.2011.07.039
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发表时间：
2011-09-16
期刊：
影响因子：
64.5
通讯作者：
Sternson, Scott M.
中科院分区：
文献类型：
--
作者：
Yang, Yunlei;Atasoy, Deniz;Sternson, Scott M.
响应生理状态变化的突触可塑性由跨多种神经元细胞类型的激素信号协调。在这里，我们结合联合收割机细胞类型特异性的电生理学，药理学和光遗传学技术来解剖神经回路和分子通路控制突触可塑性到AGRP神经元，一个人口，调节喂养。我们发现，食物剥夺提高兴奋性突触输入，这是由突触前正反馈回路涉及AMP激活的蛋白激酶介导的。谷氨酸释放的增强是由食欲激素生长激素释放肽引发的，并表现出滞后，在生长激素释放肽去除后持续数小时。持久的活动被逆转的促性腺激素瘦素，和光遗传学光刺激表明参与阿片类药物释放POMC神经元。基于这些实验，我们提出了一个记忆存储设备的生理状态构建的突触之间翻转两个持续的活动状态，通过短暂暴露于激素信号的能量水平。
Synaptic plasticity in response to changes in physiologic state is coordinated by hormonal signals across multiple neuronal cell types. Here, we combine cell-type-specific electrophysiological, pharmacological, and optogenetic techniques to dissect neural circuits and molecular pathways controlling synaptic plasticity onto AGRP neurons, a population that regulates feeding. We find that food deprivation elevates excitatory synaptic input, which is mediated by a presynaptic positive feedback loop involving AMP-activated protein kinase. Potentiation of glutamate release was triggered by the orexigenic hormone ghrelin and exhibited hysteresis, persisting for hours after ghrelin removal. Persistent activity was reversed by the anorexigenic hormone leptin, and optogenetic photostimulation demonstrated involvement of opioid release from POMC neurons. Based on these experiments, we propose a memory storage device for physiological state constructed from bistable synapses that are flipped between two sustained activity states by transient exposure to hormones signaling energy levels.