Near-Perfect Synaptic Integration by Nav1.7 in Hypothalamic Neurons Regulates Body Weight.
Near-Perfect Synaptic Integration by Nav1.7 in Hypothalamic Neurons Regulates Body Weight.
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DOI：
10.1016/j.cell.2016.05.019
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发表时间：
2016-06-16
期刊：
影响因子：
64.5
通讯作者：
Sternson SM
中科院分区：
文献类型：
--
作者：
Branco T;Tozer A;Magnus CJ;Sugino K;Tanaka S;Lee AK;Wood JN;Sternson SM
神经元非常适合毫秒时间尺度的计算，但一些神经元电路会在很长一段时间内设置行为状态，例如涉及能量稳态的行为状态。我们发现多种类型的下丘脑神经元，包括那些反向调节体重的神经元，都被专门用作近乎完美的突触积分器，可以在较长的时间尺度上求和输入。兴奋性突触后电位 (EPSP) 大大延长，比神经元膜时间常数长 10 倍。这是由于电压门控钠通道 Nav1.7 (Scn9a) 造成的，该通道以前与痛觉相关，但与突触整合无关。 AGRP、POMC 或室旁下丘脑神经元中的 Scn9a 缺失会减少小鼠 EPSP 持续时间、突触整合和体重改变。下丘脑的体内全细胞记录证实了近乎完美的突触整合。这些实验表明，Nav1.7 随着时间的推移对突触输入的整合对于体重调节至关重要，并揭示了调节长期稳态功能的回路突触控制的机制。调节体重的下丘脑神经元是近乎完美的突触整合器 在体内下丘脑神经元中观察到近乎完美的突触整合 近乎完美的突触整合取决于电压门控钠通道 Nav1.7 下丘脑神经元中 Nav1.7 的丢失会扰乱体重调节 下丘脑中的神经元能够汇总长时间接收到的突触输入，从而深入了解长期稳态功能如何就像体重维持可以通过神经回路来设定一样。
Neurons are well suited for computations on millisecond timescales, but some neuronal circuits set behavioral states over long time periods, such as those involved in energy homeostasis. We found that multiple types of hypothalamic neurons, including those that oppositely regulate body weight, are specialized as near-perfect synaptic integrators that summate inputs over extended timescales. Excitatory postsynaptic potentials (EPSPs) are greatly prolonged, outlasting the neuronal membrane time-constant up to 10-fold. This is due to the voltage-gated sodium channel Nav1.7 (Scn9a), previously associated with pain-sensation but not synaptic integration. Scn9a deletion in AGRP, POMC, or paraventricular hypothalamic neurons reduced EPSP duration, synaptic integration, and altered body weight in mice. In vivo whole-cell recordings in the hypothalamus confirmed near-perfect synaptic integration. These experiments show that integration of synaptic inputs over time by Nav1.7 is critical for body weight regulation and reveal a mechanism for synaptic control of circuits regulating long term homeostatic functions. Hypothalamic neurons that regulate body weight are near-perfect synaptic integrators Near-perfect synaptic integration is observed in hypothalamic neurons in vivo Near-perfect synaptic integration depends on the voltage-gated sodium channel Nav1.7 Loss of Nav1.7 in hypothalamic neurons disrupts regulation of body weight Neurons in the hypothalamus are capable of summing synaptic inputs received over long periods of time, providing insights into how long-term homeostatic functions like weight maintenance can be set by neural circuits.