Integrative Neuroscience Research Branch, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Confocal and Electron Microscopy Core, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Neuron. 2020 Jul 22;107(2):368-382.e8. doi: 10.1016/j.neuron.2020.04.024. Epub 2020 May 21.
The ventral tegmental area (VTA) has dopamine, GABA, and glutamate neurons, which have been implicated in reward and aversion. Here, we determined whether VTA-glutamate or -GABA neurons play a role in innate defensive behavior. By VTA cell-type-specific genetic ablation, we found that ablation of glutamate, but not GABA, neurons abolishes escape behavior in response to threatening stimuli. We found that escape behavior is also decreased by chemogenetic inhibition of VTA-glutamate neurons and detected increases in activity in VTA-glutamate neurons in response to the threatening stimuli. By ultrastructural and electrophysiological analysis, we established that VTA-glutamate neurons receive a major monosynaptic glutamatergic input from the lateral hypothalamic area (LHA) and found that photoinhibition of this input decreases escape responses to threatening stimuli. These findings indicate that VTA-glutamate neurons are activated by and required for innate defensive responses and that information on threatening stimuli to VTA-glutamate neurons is relayed by LHA-glutamate neurons.
腹侧被盖区（VTA）含有多巴胺、GABA 和谷氨酸神经元，这些神经元与奖励和厌恶有关。在这里，我们确定 VTA-谷氨酸或-GABA 神经元是否在先天防御行为中发挥作用。通过 VTA 细胞类型特异性基因消融，我们发现，谷氨酸神经元的消融而非 GABA 神经元的消融会消除对威胁性刺激的逃避行为。我们发现，化学遗传抑制 VTA 谷氨酸神经元也会降低逃避行为，并检测到 VTA 谷氨酸神经元对威胁性刺激的反应活性增加。通过超微结构和电生理分析，我们确定 VTA 谷氨酸神经元从外侧下丘脑区（LHA）接收主要的单突触谷氨酸能输入，并发现对此输入的光抑制会降低对威胁性刺激的逃避反应。这些发现表明，VTA 谷氨酸神经元被先天防御反应激活并需要，并且关于威胁性刺激的信息通过 LHA 谷氨酸神经元传递到 VTA 谷氨酸神经元。
