Hotchkiss Brain Institute and Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N4N1, Canada.
Neuron. 2011 Aug 11;71(3):529-41. doi: 10.1016/j.neuron.2011.06.006.
Changes in food availability alter the output of hypothalamic nuclei that underlie energy homeostasis. Here, we asked whether food deprivation impacts the ability of GABA synapses in the dorsomedial hypothalamus (DMH), an important integrator of satiety signals, to undergo activity-dependent changes. GABA synapses in DMH slices from satiated rats exhibit endocannabinoid-mediated long-term depression (LTD(GABA)) in response to high-frequency stimulation of afferents. When CB1Rs are blocked, however, the same stimulation elicits long-term potentiation (LTP(GABA)), which manifests presynaptically and requires heterosynaptic recruitment of NMDARs and nitric oxide (NO). Interestingly, NO signaling is required for eCB-mediated LTD(GABA). Twenty-four hour food deprivation results in a CORT-mediated loss of CB1R signaling and, consequently, GABA synapses only exhibit LTP(GABA). These observations indicate that CB1R signaling promotes LTD(GABA) and gates LTP(GABA). Furthermore, the satiety state of an animal, through regulation of eCB signaling, determines the polarity of activity-dependent plasticity at GABA synapses in the DMH.
食物供应的变化会改变下丘脑核的输出，而下丘脑核是能量平衡的基础。在这里，我们询问了饥饿是否会影响饱食信号重要整合器背内侧下丘脑 (DMH) 中 GABA 突触的活动依赖性变化。在饱食大鼠的 DMH 切片中，GABA 突触对传入神经的高频刺激会产生内源性大麻素介导的长时程抑制 (LTD(GABA))。然而，当阻断 CB1R 时，相同的刺激会引发长时程增强 (LTP(GABA))，这表现为突触前，并需要 NMDA 受体和一氧化氮 (NO) 的异突触募集。有趣的是，NO 信号对于 eCB 介导的 LTD(GABA) 是必需的。24 小时禁食会导致 CORT 介导的 CB1R 信号丢失，因此 GABA 突触仅表现出 LTP(GABA)。这些观察结果表明，CB1R 信号促进 LTD(GABA)并控制 LTP(GABA)。此外，动物的饱腹感通过调节内源性大麻素信号，决定了 DMH 中 GABA 突触活动依赖性可塑性的极性。
