Department of Cell & Molecular Biology, Tulane University, New Orleans, LA 70117.
Tulane Brain Institute, Tulane University, New Orleans, LA 70118.
eNeuro. 2017 Sep 19;4(5). doi: 10.1523/ENEURO.0216-17.2017. eCollection 2017 Sep-Oct.
Glucocorticoids rapidly stimulate endocannabinoid synthesis and modulation of synaptic transmission in hypothalamic neuroendocrine cells via a nongenomic signaling mechanism. The endocannabinoid actions are synapse-constrained by astrocyte restriction of extracellular spatial domains. Exogenous cannabinoids have been shown to modulate postsynaptic potassium currents, including the A-type potassium current (), in different cell types. The activity of magnocellular neuroendocrine cells is shaped by a prominent . We tested for a rapid glucocorticoid modulation of the postsynaptic and in magnocellular neuroendocrine cells of the hypothalamic paraventricular nucleus (PVN) using whole-cell recordings in rat brain slices. Application of the synthetic glucocorticoid dexamethasone (Dex) had no rapid effect on the or amplitude, voltage dependence, or kinetics in magnocellular neurons in slices from untreated rats. In magnocellular neurons from salt-loaded rats, however, Dex application caused a rapid suppression of the and a depolarizing shift in voltage dependence. Exogenously applied endocannabinoids mimicked the rapid Dex modulation of the , and CB1 receptor antagonists and agonists blocked and occluded the Dex-induced changes in the , respectively, suggesting an endocannabinoid dependence of the rapid glucocorticoid effect. Preincubation of control slices in a gliotoxin resulted in the partial recapitulation of the glucocorticoid-induced rapid suppression of the . These findings demonstrate a glucocorticoid suppression of the postsynaptic in PVN magnocellular neurons via an autocrine endocannabinoid-dependent mechanism following chronic dehydration, and suggest a possible role for astrocytes in the control of the autocrine endocannabinoid actions.
糖皮质激素通过非基因组信号机制快速刺激下丘脑神经内分泌细胞中的内源性大麻素合成和突触传递的调制。内源性大麻素的作用受到星形胶质细胞对细胞外空间域的限制的限制。已经表明外源性大麻素可以调节不同细胞类型的突触后钾电流，包括 A 型钾电流 (). 大细胞神经内分泌细胞的活动由突出的 塑造。我们使用大鼠脑切片中的全细胞膜片钳记录来测试快速糖皮质激素对下丘脑室旁核 (PVN) 大细胞神经内分泌细胞的突触后 和 的调制。合成糖皮质激素地塞米松 (Dex) 的应用对未经处理的大鼠脑切片中大细胞神经元中的 或 幅度、电压依赖性或动力学没有快速作用。然而，在盐负荷大鼠的大细胞神经元中，Dex 的应用导致 快速抑制和 电压依赖性的去极化偏移。外源性内源性大麻素模拟了 Dex 对 的快速调制，而 CB1 受体拮抗剂和激动剂分别阻断和封闭了 Dex 诱导的 变化，表明快速糖皮质激素效应依赖于内源性大麻素。在对照切片中用神经胶质毒素预孵育导致糖皮质激素诱导的快速抑制 部分重现。这些发现表明，慢性脱水后，通过自分泌内源性大麻素依赖性机制，糖皮质激素抑制了 PVN 大细胞神经元中的突触后 ，并表明星形胶质细胞可能在控制自分泌内源性大麻素作用中起作用。
