Acute Aversive Stimuli Rapidly Increase the Activity of Ventral Tegmental Area Dopamine Neurons in Awake Mice

Neuroscience. 2018 Aug 21;386:16-23. doi: 10.1016/j.neuroscience.2018.06.027. Epub 2018 Jun 27.


The ventral tegmental area (VTA) is one of the origins of the brain dopaminergic system and is involved in regulating various physiological functions such as pain processing and motivation. In this study, we utilized a fiber photometry system to specifically investigate the activity of dopamine neurons in the VTA using dopamine transporter promoter-driven Cre recombinase-expressing mice and site-specific infection of adeno-associated virus carrying the FLEX G-CaMP6 gene. As expected, expression of G-CaMP6 was restricted to VTA dopamine neurons. We recorded G-CaMP6 green fluorescent signal, which reflected dopaminergic neuronal activity, in awake mice exposed to tail pinch, ultrasonic sound, predator odor, and a male intruder mouse. These stimuli resulted in a rapid and short-lasting increase in the activity of VTA dopamine neurons while the control stimuli of a gentle tail touch and appearance of empty box did not induce any changes. In addition, fluorescence intensity was not changed by any of these stimuli in the control animals expressing hrGFP instead of G-CaMP6 in VTA dopamine neurons. Our data clearly show that acute aversive stimuli rapidly increase the activity of VTA dopamine neurons and thus suggest a salience-processing role.

Keywords: G-CaMP6; fiber photometry; intruder mouse; predator odor; tail pinch; ultrasonic sound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / adverse effects*
  • Animals
  • Dopaminergic Neurons / metabolism*
  • Male
  • Mice
  • Mice, Transgenic
  • Odorants
  • Physical Stimulation / adverse effects
  • Ventral Tegmental Area / metabolism*
  • Wakefulness / physiology*