Neuron
Volume 107, Issue 2, 22 July 2020, Pages 368-382.e8
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Article
VTA Glutamatergic Neurons Mediate Innate Defensive Behaviors

https://doi.org/10.1016/j.neuron.2020.04.024Get rights and content
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Highlights

  • Ventral tegmental area (VTA)-glutamate neurons encode innate defensive behavior

  • A single VTA-glutamate neuron receives multiple hypothalamic excitatory inputs

  • Hypothalamic excitatory inputs to VTA-glutamate neurons convey treating information

Summary

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.

Keywords

VTA
VTA-VGluT2 neurons
VTA-GABA neurons
innate escape behavior
looming
predator odor
threatening stimuli
VTA calcium imaging
lateral hypothalamic area

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