Periaqueductal efferents to dopamine and GABA neurons of the VTA

PLoS One. 2018 Jan 5;13(1):e0190297. doi: 10.1371/journal.pone.0190297. eCollection 2018.


Neurons in the periaqueductal gray (PAG) modulate threat responses and nociception. Activity in the ventral tegmental area (VTA) on the other hand can cause reinforcement and aversion. While in many situations these behaviors are related, the anatomical substrate of a crosstalk between the PAG and VTA remains poorly understood. Here we describe the anatomical and electrophysiological organization of the VTA-projecting PAG neurons. Using rabies-based, cell type-specific retrograde tracing, we observed that PAG to VTA projection neurons are evenly distributed along the rostro-caudal axis of the PAG, but concentrated in its posterior and ventrolateral segments. Optogenetic projection targeting demonstrated that the PAG-to-VTA pathway is predominantly excitatory and targets similar proportions of Ih-expressing VTA DA and GABA neurons. Taken together, these results set the framework for functional analysis of the interplay between PAG and VTA in the regulation of reward and aversion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Female
  • GABAergic Neurons / metabolism*
  • Male
  • Mice
  • Ventral Tegmental Area / metabolism*
  • Ventral Tegmental Area / physiology


  • Dopamine

Grant support

This study was supported by the Swiss National Science Foundation (310030_149985) ( and by the Fondation Privée des Hopitaux Universitaires de Genève ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.