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

Despite abundant evidence that dopamine (DA) modulates medial prefrontal cortex (mPFC) activity to mediate diverse behavioral functions(1,2), the precise circuit computations remain elusive. One potentially unifying model by which DA can underlie a diversity of functions is to modulate the signal-to-noise ratio (SNR) in subpopulations of mPFC neurons(3–6), where neural activity conveying sensory information (signal) is amplified relative to spontaneous firing (noise). Here, we demonstrate that DA increases the SNR of responses to aversive stimuli in mPFC neurons projecting to the dorsal periaqueductal gray (dPAG). Using electrochemical approaches, we reveal the precise time course of pinch-evoked DA release in the mPFC, and show that mPFC DA biases behavioral responses to aversive stimuli. Activation of mPFC-dPAG neurons is sufficient to drive place avoidance and defensive behaviors. mPFC-dPAG neurons displayed robust shock-induced excitations, as visualized by single-cell, projection-defined microendoscopic calcium imaging. Finally, photostimulation of DA terminals in the mPFC revealed an increase in SNR in mPFC-dPAG responses to aversive stimuli. Together, these data highlight how mPFC DA can route sensory information in a valence-specific manner to different downstream circuits.