Sleep Deprivation Distinctly Alters Glutamate Transporter 1 Apposition and Excitatory Transmission to Orexin and MCH Neurons
Sleep Deprivation Distinctly Alters Glutamate Transporter 1 Apposition and Excitatory Transmission to Orexin and MCH Neurons
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DOI：
10.1523/jneurosci.2179-17.2018
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发表时间：
2018-03-07
影响因子：
5.3
通讯作者：
Semba, Kazue
中科院分区：
文献类型：
--
作者：
Briggs, Chantalle;Hirasawa, Michiru;Semba, Kazue
谷氨酸转运体1（Glutamate Transporter 1，GLT 1）是主要的星形胶质细胞转运体，在脑内形成谷氨酸能传递。然而，这种转运蛋白是否调节睡眠-觉醒调节神经元尚不清楚。使用定量免疫组织化学分析，我们评估了体周GLT 1沉积与睡眠-觉醒神经元在雄性大鼠6小时睡眠剥夺（SD）或6小时不受干扰的条件下，当动物大多睡着了（休息）。我们发现，与休息相比，SD降低了下丘脑外侧部中与唤醒促进食欲素神经元的体周GLT 1沉积。GLT 1沉积减少与紧张性突触前抑制兴奋性传输到这些神经元由于组III代谢型谷氨酸受体的激活，GLT 1抑制剂在休息条件下模仿的效果。与此相反，SD导致GLT 1与外侧下丘脑中促进睡眠的黑色素浓集激素（MCH）神经元的沉积增加。在功能上，这降低了MCH神经元对高频突触激活的突触后反应，而不改变突触前谷氨酸的释放。GLT 1与食欲素和MCH神经元的沉积变化在6 h SD后3 h睡眠机会后逆转。这些SD的影响是特定的食欲素和MCH神经元，在GLT 1的沉积没有变化，在基底前脑胆碱能或小清蛋白阳性GABA神经元。因此，在一个单一的下丘脑区域，GLT 1差异调节兴奋性传输到唤醒和睡眠促进神经元取决于睡眠的历史。这些过程可能构成新的星形胶质细胞介导的稳态机制控制睡眠-觉醒行为。
Glutamate transporter 1 (GLT1) is the main astrocytic transporter that shapes glutamatergic transmission in the brain. However, whether this transporter modulates sleep-wake regulatory neurons is unknown. Using quantitative immunohistochemical analysis, we assessed perisomatic GLT1 apposition with sleep-wake neurons in the male rat following 6 h sleep deprivation (SD) or following 6 h undisturbed conditions when animals were mostly asleep (Rest). We found that SD decreased perisomatic GLT1 apposition with wake-promoting orexin neurons in the lateral hypothalamus compared with Rest. Reduced GLT1 apposition was associated with tonic presynaptic inhibition of excitatory transmission to these neurons due to the activation of Group III metabotropic glutamate receptors, an effect mimicked by a GLT1 inhibitor in the Rest condition. In contrast, SD resulted in increased GLT1 apposition with sleep-promoting melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus. Functionally, this decreased the postsynaptic response of MCH neurons to high-frequency synaptic activation without changing presynaptic glutamate release. The changes in GLT1 apposition with orexin and MCH neurons were reversed after 3 h of sleep opportunity following 6 h SD. These SD effects were specific to orexin and MCH neurons, as no change in GLT1 apposition was seen in basal forebrain cholinergic or parvalbumin-positive GABA neurons. Thus, within a single hypothalamic area, GLT1 differentially regulates excitatory transmission to wake-and sleep-promoting neurons depending on sleep history. These processes may constitute novel astrocyte-mediated homeostatic mechanisms controlling sleep-wake behavior.