Aversive experiences induce valence plasticity of instructive signals to change future learning rules in mice.

Aversive signals such as pain serve an instructive role in aversive learning to promote animal survival. While negative valence of aversive signals is considered to be innately assigned, the valence can be scaled by internal state and previous experiences. However, the neuronal mechanisms underlying state and experience-dependent valence modulation remain unexplored. Previous studies demonstrated synaptic potentiation in instructive signal pathways following robust aversive learning. Here, we hypothesized that long-term potentiation (LTP) in the parabrachial-to-central amygdala (PB-CeC/L) pathway, an important nociceptive circuit for producing pain and emotional learning, enhances the negative valence and thereby alter future learning rules. To test this hypothesis, we developed pathway-specific in vivo LTP induction methods and mathematical models. Our results suggest that LTP in the PB-CeC/L pathway alters aversive valence and future learning rules by enhancing subsequent learning and memory generalization. These results may help to identify a therapeutic target for post-traumatic stress disorder.