GluA2-Lacking AMPA Receptors and Nitric Oxide Signaling Gate Spike-Timing-Dependent Potentiation of Glutamate Synapses in the Dorsal Raphe Nucleus.
GluA2-Lacking AMPA Receptors and Nitric Oxide Signaling Gate Spike-Timing-Dependent Potentiation of Glutamate Synapses in the Dorsal Raphe Nucleus.
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DOI：
10.1523/eneuro.0116-17.2017
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发表时间：
2017-05
期刊：
影响因子：
3.4
通讯作者：
Shen RY
中科院分区：
文献类型：
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作者：
Haj-Dahmane S;Béïque JC;Shen RY
中缝背核(DRN)从控制DRN 5-羟色胺(5-HT)神经元功能的许多脑区接受谷氨酸能输入。通过整合这些突触输入，5-羟色胺神经元调节过多的行为和生理功能。然而，对DRN 5-HT神经元的兴奋性输入是否可以经历活动依赖性的强度变化，以及控制其可塑性的机制仍不清楚。在这里，我们描述了一种新的形式的谷氨酸突触对大鼠DRN 5-HT神经元的尖峰时序依赖的长时程增强(TLTP)。这种形式的突触可塑性是由突触后细胞内钙的增加启动的，但通过谷氨酸释放的可能性的持续增加来维持。谷氨酸突触与DRN 5-羟色胺的TLTP不依赖于NMDA受体，但需要钙通透性AMPA受体和电压依赖性钙通道的激活。TLTP的突触前表达是由逆行信使一氧化氮(NO)和cGMP/PKG通路激活介导的。综上所述，这些结果表明，DRN中的谷氨酸突触经历了由NO信号调控的活性依赖的突触可塑性，并揭示了NO在DRN中控制突触功能和可塑性中先前未知的作用。
The dorsal raphe nucleus (DRn) receives glutamatergic inputs from numerous brain areas that control the function of DRn serotonin (5-HT) neurons. By integrating these synaptic inputs, 5-HT neurons modulate a plethora of behaviors and physiological functions. However, it remains unknown whether the excitatory inputs onto DRn 5-HT neurons can undergo activity-dependent change of strength, as well as the mechanisms that control their plasticity. Here, we describe a novel form of spike-timing–dependent long-term potentiation (tLTP) of glutamate synapses onto rat DRn 5-HT neurons. This form of synaptic plasticity is initiated by an increase in postsynaptic intracellular calcium but is maintained by a persistent increase in the probability of glutamate release. The tLTP of glutamate synapses onto DRn 5-HT is independent of NMDA receptors but requires the activation of calcium-permeable AMPA receptors and voltage-dependent calcium channels. The presynaptic expression of the tLTP is mediated by the retrograde messenger nitric oxide (NO) and activation of cGMP/PKG pathways. Collectively, these results indicate that glutamate synapses in the DRn undergo activity-dependent synaptic plasticity gated by NO signaling and unravel a previously unsuspected role of NO in controlling synaptic function and plasticity in the DRn.