VTA Glutamatergic Neurons Mediate Innate Defensive Behaviors

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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aggression / physiology*
  • Animals
  • Escape Reaction
  • Glutamic Acid / physiology*
  • Humans
  • Hypothalamic Area, Lateral / cytology
  • Hypothalamic Area, Lateral / physiology
  • Hypothalamus / cytology
  • Hypothalamus / physiology
  • Mice
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Optogenetics
  • Photic Stimulation
  • Reflex, Monosynaptic / physiology
  • Ventral Tegmental Area / cytology*
  • Ventral Tegmental Area / physiology*
  • Ventral Tegmental Area / ultrastructure
  • gamma-Aminobutyric Acid / physiology


  • Glutamic Acid
  • gamma-Aminobutyric Acid