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

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.