Functional Principles of Posterior Septal Inputs to the Medial Habenula.

Functional Principles of Posterior Septal Inputs to the Medial Habenula.
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DOI:
10.1016/j.celrep.2017.12.064
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发表时间:
2018-01-16
期刊:
影响因子:
8.8
通讯作者:
Diana MA
Diana MA
中科院分区:
生物学1区
文献类型:
--
作者:
Otsu Y;Lecca S;Pietrajtis K;Rousseau CV;Marcaggi P;Dugué GP;Mailhes-Hamon C;Mameli M;Diana MA

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medial habenula (MHb)是一个上皮中枢,通过连接前脑区域和中脑单胺能中枢,参与厌恶状态的表达和消除。尽管关于它们的突触特性存在矛盾的信息,但从后隔向MHb的兴奋性输入的生理学仍然难以捉摸。在这里,结合光遗传学定位与体内和体外生理学,我们研究了后间隔传入到MHb的突触特性以及它们如何影响行为。我们证明MHb细胞通过钙渗透性α-氨基-3-羟基-5-甲基-4-异唑丙酸(AMPA)、异三聚体GluN2A-GluN2B-GluN1 n -甲基- d -天冬氨酸(NMDA)受体和抑制性II组代谢型谷氨酸受体接受稀疏输入,产生纯粹的谷氨酸能反应。我们描述了这些成分通过MHb细胞的复杂整合动力学。最后,我们将离体数据与体内记录的真实传入放电模式结合起来,证明MHb中有效的光遗传中隔刺激可诱导焦虑缓解并促进运动,为中隔-小窝通路的重要性提供了期待已久的证据。内侧束(MHb)神经元接受来自后隔(PS)的稀疏输入,以纯谷氨酸模式将PS传入MHb,兴奋性嗜离子性和抑制性代谢受体在MHb中传递PS输入,MHb中的PS激活增加运动并诱导焦虑缓解,内侧束(MHb)通过连接前脑区域和中脑单胺能中枢参与厌恶状态的表达。在这里,Otsu等人提供了从突触生理学到行为结果的综合表征,从后中隔的谷氨酸能传入,表明中隔刺激MHb促进运动和焦虑缓解。
The medial habenula (MHb) is an epithalamic hub contributing to expression and extinction of aversive states by bridging forebrain areas and midbrain monoaminergic centers. Although contradictory information exists regarding their synaptic properties, the physiology of the excitatory inputs to the MHb from the posterior septum remains elusive. Here, combining optogenetics-based mapping with ex vivo and in vivo physiology, we examine the synaptic properties of posterior septal afferents to the MHb and how they influence behavior. We demonstrate that MHb cells receive sparse inputs producing purely glutamatergic responses via calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), heterotrimeric GluN2A-GluN2B-GluN1 N-methyl-D-aspartate (NMDA) receptors, and inhibitory group II metabotropic glutamate receptors. We describe the complex integration dynamics of these components by MHb cells. Finally, we combine ex vivo data with realistic afferent firing patterns recorded in vivo to demonstrate that efficient optogenetic septal stimulation in the MHb induces anxiolysis and promotes locomotion, contributing long-awaited evidence in favor of the importance of this septo-habenular pathway. Medial habenular (MHb) neurons receive sparse inputs from the posterior septum (PS) PS afferents to the MHb function in a purely glutamatergic mode Excitatory ionotropic and inhibitory metabotropic receptors convey PS inputs in the MHb PS activation in the MHb increases locomotion and induces anxiolysis The medial habenula (MHb) contributes to aversive state expression by linking forebrain areas to midbrain monoaminergic centers. Here, Otsu et al. provide a comprehensive characterization, from synaptic physiology to behavioral outcomes, of its glutamatergic afferents from the posterior septum, suggesting that septal stimulation in the MHb promotes locomotion and anxiolysis.
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