Dopamine enhances signal-to-noise ratio in cortical-brainstem encoding of aversive stimuli

Nature. 2018 Nov;563(7731):397-401. doi: 10.1038/s41586-018-0682-1. Epub 2018 Nov 7.

Abstract

Dopamine modulates medial prefrontal cortex (mPFC) activity to mediate diverse behavioural functions1,2; however, the precise circuit computations remain unknown. One potentially unifying model by which dopamine may underlie a diversity of functions is by modulating the signal-to-noise ratio in subpopulations of mPFC neurons3-6, where neural activity conveying sensory information (signal) is amplified relative to spontaneous firing (noise). Here we demonstrate that dopamine increases the signal-to-noise ratio of responses to aversive stimuli in mPFC neurons projecting to the dorsal periaqueductal grey (dPAG). Using an electrochemical approach, we reveal the precise time course of pinch-evoked dopamine release in the mPFC, and show that mPFC dopamine biases behavioural responses to aversive stimuli. Activation of mPFC-dPAG neurons is sufficient to drive place avoidance and defensive behaviours. mPFC-dPAG neurons display robust shock-induced excitations, as visualized by single-cell, projection-defined microendoscopic calcium imaging. Finally, photostimulation of dopamine terminals in the mPFC reveals an increase in the signal-to-noise ratio in mPFC-dPAG responses to aversive stimuli. Together, these data highlight how dopamine in the mPFC can selectively route sensory information to specific downstream circuits, representing a potential circuit mechanism for valence processing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / physiology*
  • Calcium Signaling
  • Dopamine / metabolism*
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways
  • Periaqueductal Gray / cytology*
  • Periaqueductal Gray / physiology*
  • Prefrontal Cortex / cytology*
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Long-Evans
  • Signal-To-Noise Ratio
  • Single-Cell Analysis
  • Tail

Substances

  • Dopamine