Optogenetic LTP Manipulation and Mathematical Modeling to Investigate Value Plasticity of the Instructive Signal in Mice.

Adaptive behaviors shaped by prior experience are essential for increasing animal survival. Aversive experiences play a pivotal role in memory formation and in updating subsequent learning rules. While the negative value of aversive signals, which are both necessary and sufficient to drive a conditioned response, is considered to be innately specified, it can also be subject to experience-dependent scaling. Previous reports demonstrated synaptic potentiation in nociceptive pathways following robust aversive learning. However, the neuronal basis of experience-dependent value updating remains largely unknown. Recently, we demonstrated that long-term potentiation (LTP) in the parabrachial-central amygdala (PB-CeA) pathway, an important circuit involved in pain processing and aversive learning, enhances the negative value and thereby updates future learning rules. Here, we present a protocol that combines behavioral analysis using pathway-specific optogenetic induction of in vivo LTP with mathematical modeling to examine value modification using Bayesian inference of the unconditioned stimulus value using the Rescorla-Wagner model. This protocol enables investigation of the mechanisms underlying experience-dependent value modulation and learning-rule changes in mice. Potentially, this protocol may provide a framework for understanding learning rules across a wide range of species and for the development of treatments for stress-related disorders. Key features • This protocol enables pathway-specific in vivo LTP induction to investigate the causal relationship between synaptic plasticity and behavioral outputs. • The protocol combines behavioral manipulation with computational modeling to interpret value plasticity of the instructive signal in terms of learning-rule updating via circuit-level plasticity.