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）具有多巴胺，GABA和谷氨酸神经元，它们与奖励和厌恶有关。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起作用。通过VTA细胞类型特定的遗传消融，我们发现，对谷氨酸而不是GABA的消融消除了对威胁性刺激的逃逸行为。我们发现，通过对VTA谷氨酸神经元的化学生成抑制作用，逃逸行为也降低了，并检测到VTA谷氨酸神经元对威胁性刺激的活性增加。通过超微结构和电生理分析，我们建立了VTA-谷氨酸神经元从下丘脑外侧区域（LHA）接收主要的单突触性谷氨酸能输入的方法，并发现该输入的光抑制作用降低了对威胁性刺激的逃逸反应。这些发现表明，先天的防御反应激活了VTA-谷氨酸神经元，并需要先天的防御反应，并且LHA-谷氨酸神经元传递了有关对VTA-谷氨酸神经元的威胁刺激的信息。