Department of Neurobiology & Anatomy, University of Texas Medical School, Houston, Texas 77030, USA.
J Neurosci. 2011 Jun 22;31(25):9222-30. doi: 10.1523/JNEUROSCI.0531-11.2011.
Inhibitory neurons in the thalamic reticular nucleus (TRN) play a critical role in controlling information transfer between thalamus and neocortex. GABAergic synapses formed by TRN neurons contact both thalamic relay cells and neurons within TRN. These two types of synapses are thought to have distinct roles for the generation of thalamic network activity, but their selective regulation is poorly understood. In many areas throughout the brain, retrograde signaling mediated by endocannabinoids acts to dynamically regulate synaptic strength over both short and long time scales. However, retrograde signaling has never been demonstrated in the thalamus. Here, we show that depolarization-induced suppression of inhibition (DSI) is prominent at inhibitory synapses interconnecting TRN neurons. DSI is completely abolished in the presence of a cannabinoid receptor 1 (CB1R) antagonist and in mice lacking CB1Rs. DSI is prevented by DAG lipase inhibitors and prolonged by blocking the 2-arachidonoylglycerol (2-AG) degradation enzyme monoacylglycerol lipase, indicating that it is mediated by the release of 2-AG from TRN neurons. By contrast, DSI is not observed at TRN synapses targeting thalamic relay neurons. A combination of pharmacological and immunohistochemical data indicate that the differences in endocannabinoid signaling at the two synapses are mediated by a synapse-specific targeting of CB1Rs, as well as differences in endocannabinoid release between the two target neurons. Together, our results show that endocannabinoids control transmitter release at specific thalamic synapses, and could dynamically regulate sensory information processing and thalamus-mediated synchronous oscillations.
丘脑网状核（TRN）中的抑制性神经元在控制丘脑和新皮层之间的信息传递方面起着关键作用。TRN 神经元形成的 GABA 能突触既与丘脑中继细胞接触，也与 TRN 内的神经元接触。这两种类型的突触被认为对丘脑网络活动的产生具有不同的作用，但它们的选择性调节知之甚少。在大脑的许多区域，内源性大麻素介导的逆行信号作用于在短时间和长时间尺度上动态调节突触强度。然而，逆行信号从未在丘脑上得到证明。在这里，我们表明，在连接 TRN 神经元的抑制性突触中，去极化诱导的抑制（DSI）非常明显。在存在大麻素受体 1（CB1R）拮抗剂和缺乏 CB1R 的小鼠中，DSI 完全被消除。DSI 被二酰基甘油脂肪酶抑制剂阻止，并通过阻断 2-花生四烯酸甘油（2-AG）降解酶单酰基甘油脂肪酶而延长，表明它是由 TRN 神经元释放 2-AG 介导的。相比之下，在靶向丘脑中继神经元的 TRN 突触上观察不到 DSI。药理学和免疫组织化学数据的组合表明，两种突触中内源性大麻素信号的差异是由 CB1R 的突触特异性靶向以及两种靶神经元之间内源性大麻素释放的差异介导的。总之，我们的结果表明，内源性大麻素控制特定丘脑突触的递质释放，并可以动态调节感觉信息处理和丘脑介导的同步振荡。
