Punishment history biases corticothalamic responses to motivationally-significant stimuli

Making predictions about future rewards or punishments is fundamental to adaptive behavior. These processes are influenced by prior experience. For example, prior exposure to aversive stimuli or stressors changes behavioral responses to negative- and positive-value predictive cues. Here, we demonstrate a role for medial prefrontal cortex (mPFC) neurons projecting to the paraventricular nucleus of the thalamus (PVT; mPFC[->]PVT) in this process. We found that a history of punishments negatively biased behavioral responses to motivationally-relevant stimuli in mice and that this negative bias was associated with hyperactivity in mPFC[->]PVT neurons during exposure to those cues. Furthermore, artificially mimicking this hyperactive response with selective optogenetic excitation of the same pathway recapitulated the punishmentinduced negative behavioral bias. Together, our results highlight how information flow within the mPFC[->]PVT circuit is critical for making predictions about imminent motivationally-relevant outcomes as a function of prior experience.