A VTA GABAergic Neural Circuit Mediates Visually Evoked Innate Defensive Responses

• Published in: Neuron (Cambridge, Mass.) Mass.), 2019-08, Vol.103 (3), p.473-488.e6
• Main Authors: Zhou, Zheng, Liu, Xuemei, Chen, Shanping, Zhang, Zhijian, Liu, Yuanming, Montardy, Quentin, Tang, Yongqiang, Wei, Pengfei, Liu, Nan, Li, Lei, Song, Ru, Lai, Juan, He, Xiaobin, Chen, Chen, Bi, Guoqiang, Feng, Guoping, Xu, Fuqiang, Wang, Liping
• Format: Article
• Language: English
• Subjects: Afferent Pathways - physiology; Amygdala; Animals; Aversion; Behavior; Calcium Signaling; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - physiology; Central Amygdaloid Nucleus - physiology; Defensive behavior; defensive responses; Escape Reaction - physiology; Fear - physiology; GABAergic neurons; GABAergic Neurons - physiology; gamma-Aminobutyric Acid - physiology; Genes, Reporter; Glutamatergic transmission; Glutamic Acid - physiology; innate fear; Laboratories; looming; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins - physiology; Neurons; Neurosciences; Optogenetics; Photic Stimulation; Photoactivation; Proto-Oncogene Proteins c-fos - analysis; Superior colliculus; Synapses; ventral tegmental area; Ventral Tegmental Area - physiology; Ventral tegmentum; γ-Aminobutyric acid
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2019.05.027

Innate defensive responses are essential for animal survival and are conserved across species. The ventral tegmental area (VTA) plays important roles in learned appetitive and aversive behaviors, but whether it plays a role in mediating or modulating innate defensive responses is currently unknown. We report that VTAGABA+ neurons respond to a looming stimulus. Inhibition of VTAGABA+ neurons reduced looming-evoked defensive flight behavior, and photoactivation of these neurons resulted in defense-like flight behavior. Using viral tracing and electrophysiological recordings, we show that VTAGABA+ neurons receive direct excitatory inputs from the superior colliculus (SC). Furthermore, we show that glutamatergic SC-VTA projections synapse onto VTAGABA+ neurons that project to the central nucleus of the amygdala (CeA) and that the CeA is involved in mediating the defensive behavior. Our findings demonstrate that aerial threat-related visual information is relayed to VTAGABA+ neurons mediating innate behavioral responses, suggesting a more general role of the VTA. [Display omitted] •VTAGABA+ neurons mediate looming-evoked innate defensive responses•SC activates VTAGABA+ neurons and mediates innate defensive behaviors•CeA is a downstream target of the SC-VTAGABA+ pathway•CeA-projecting VTAGABA+ involved in looming-evoked defensive behaviors Zhou et al. identified a neural circuit related to VTAGABA+ neurons that mediates visually evoked innate defensive responses, involving the SCGlut+- VTAGABA+-CeA pathway.