Extracellular glucose-dependent IPSC enhancement by leptin in fast-spiking to pyramidal neuron connections via JAK2-PI3K pathway in the rat insular cortex
Extracellular glucose-dependent IPSC enhancement by leptin in fast-spiking to pyramidal neuron connections via JAK2-PI3K pathway in the rat insular cortex
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DOI：
10.1016/j.neuropharm.2019.02.021
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发表时间：
2019-05-01
影响因子：
4.7
通讯作者：
Kobayashi, Masayuki
中科院分区：
文献类型：
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作者：
Murayama, Shota;Yamamoto, Kiyofumi;Kobayashi, Masayuki
瘦素在脂肪细胞中产生，并通过控制食欲和代谢在调节能量平衡中起关键作用。瘦素受体广泛分布于大脑中，尤其是下丘脑、海马和新皮质。岛叶皮层（IC）处理味觉和内脏信息，这些信息在功能上与摄食行为相关。然而，瘦素是否以及如何调节IC神经活动仍然是一个悬而未决的问题。我们的配对全细胞膜片钳记录使用IC切片的准备工作表明，单一抑制性突触后电流（uIPSC），但不是uEPSC增强瘦素之间的连接锥体（PN）和快速尖峰神经元（FSN）。leptin诱导的uIPSC振幅的增加伴随着成对脉冲比的降低。在JAK 2-PI 3 K而不是MAPK通路的抑制剂的应用下，瘦素不改变uIPSC振幅。方差-均值分析表明，瘦素增加释放概率，但不增加释放位点的数量和量子大小。这些电生理结果表明，leptin诱导的uIPSC增加是通过激活突触前FSN中的JAK 2-PI 3 K通路介导的。在体光学成像显示，瘦素的应用减少了IC的电刺激引起的兴奋性传播IC。这些瘦素诱导的效果没有观察到低能量状态下：低葡萄糖浓度（2.5 mM）在体外和一天禁食条件下在体内。然而，瘦素增强uIPSCs在应用低葡萄糖与AMPK抑制剂。这些结果表明，瘦素通过促进FSN -> PN连接中的GABA释放来抑制IC兴奋，这在饥饿状态下可能不会发生。
Leptin is produced in the adipocytes and plays a pivotal role in regulation of energy balance by controlling appetite and metabolism. Leptin receptors are widely distributed in the brain, especially in the hypothalamus, hippocampus, and neocortex. The insular cortex (IC) processes gustatory and visceral information, which functionally correlate to feeding behavior. However, it is still an open issue whether and how leptin modulates IC neural activities. Our paired whole-cell patch-clamp recordings using IC slice preparations demonstrated that unitary inhibitory postsynaptic currents (uIPSCs) but not uEPSCs were potentiated by leptin in the connections between pyramidal (PNs) and fast-spiking neurons (FSNs). The leptin-induced increase in uIPSC amplitude was accompanied by a decrease in paired-pulse ratio. Under application of inhibitors of JAK2-PI3K but not MAPK pathway, leptin did not change uIPSC amplitude. Variance-mean analysis revealed that leptin increased the release probability but not the quantal size and the number of release site. These electrophysiological findings suggest that the leptin-induced uIPSC increase is mediated by activation of JAK2-PI3K pathway in presynaptic FSNs. An in vivo optical imaging revealed that leptin application decreased excitatory propagation in IC induced by electrical stimulation of IC. These leptin-induced effects were not observed under the low energy states: low glucose concentration (2.5 mM) in vitro and one-day-fasting condition in vivo. However, leptin enhanced uIPSCs under application of low glucose with an AMPK inhibitor. These results suggest that leptin suppresses IC excitation by facilitating GABA release in FSN -> PN connections, which may not occur under a hunger state.