Department of Biological Sciences, Konkuk University, Seoul, 05029, South Korea.
Department of Biological Sciences, Konkuk University, Seoul, 05029, South Korea.
Neuropharmacology. 2020 Dec 1;180:108295. doi: 10.1016/j.neuropharm.2020.108295. Epub 2020 Sep 1.
Neuropeptide Y (NPY) is one of peptide neuromodulators, well known for orexigenic, anxiolytic and antidepressant effects. We previously reported that NPY decreases GABAergic transmission in the lateral habenula (LHb). In the current study, we aim to investigate the underlying signaling pathways that mediate inhibitory action of NPY in the LHb by employing whole-cell patch clamp recording with pharmacological interventions. Here, we revealed that Y1 receptors (Y1Rs) but not Y2Rs mediate NPY-induced decrease of GABAergic transmission in the LHb. Surprisingly, NPY-induced decrease of inhibitory transmission in the LHb was not dependent on adenylyl cyclase (AC)/protein kinase A (PKA)-dependent pathway as reported in other brain areas. Instead, pharmacological blockade of phospholipase C (PLC) or protein kinase C (PKC) activity abolished the decrease of GABAergic transmission by NPY in the LHb. Our findings suggest that Y1Rs in the LHb may trigger the activation of PLC/PKC-dependent pathway but not the classical AC/PKA-dependent pathway to decrease inhibitory transmission of the LHb.
神经肽 Y（NPY）是一种肽类神经调质，以其食欲刺激、抗焦虑和抗抑郁作用而闻名。我们之前曾报道过 NPY 可降低外侧缰核（LHb）中的 GABA 能传递。在本研究中，我们通过药理学干预的全细胞膜片钳记录，旨在研究介导 NPY 在 LHb 中抑制作用的潜在信号通路。在这里，我们揭示了 Y1 受体（Y1Rs）而不是 Y2 受体介导 NPY 诱导的 LHb 中 GABA 能传递的减少。令人惊讶的是，与在其他脑区报道的情况不同，NPY 诱导的 LHb 中抑制性传递的减少不依赖于腺苷酸环化酶（AC）/蛋白激酶 A（PKA）依赖性途径。相反，PLC 或 PKC 活性的药理学阻断可消除 NPY 在 LHb 中对 GABA 能传递的抑制作用。我们的研究结果表明，LHb 中的 Y1R 可能触发 PLC/PKC 依赖性途径的激活，而不是经典的 AC/PKA 依赖性途径，以降低 LHb 的抑制性传递。
