A VTA GABAergic Neural Circuit Mediates Visually Evoked Innate Defensive Responses

Neuron. 2019 Aug 7;103(3):473-488.e6. doi: 10.1016/j.neuron.2019.05.027. Epub 2019 Jun 12.

Abstract

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.

Keywords: GABAergic neurons; defensive responses; innate fear; looming; superior colliculus; ventral tegmental area.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Afferent Pathways / physiology
  • Animals
  • Calcium Signaling
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / physiology
  • Central Amygdaloid Nucleus / physiology
  • Escape Reaction / physiology*
  • Fear / physiology*
  • GABAergic Neurons / physiology*
  • Genes, Reporter
  • Glutamic Acid / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / physiology
  • Optogenetics
  • Photic Stimulation
  • Proto-Oncogene Proteins c-fos / analysis
  • Ventral Tegmental Area / physiology*
  • gamma-Aminobutyric Acid / physiology

Substances

  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins c-fos
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2