Opposing reward-epoch population coding in anterior insular cortex dissociates sign- and goal-tracking despite equivalent conditioned responding
Year: 2026
Type: preprint
Abstract: When Pavlovian lever cues predict reward, rats diverge in how they express learned associations: sign-tracking (ST) rats approach and engage the cue with greater persistence, while goal-tracking (GT) rats approach the reward site and are more consistently outcome-sensitive. The anterior insular cortex (aIC) and its interactions with amygdala and striatal regions are differentially recruited across phenotypes, implicating aIC as a node where associative strategy diverges at the circuit level. To characterize this neural divergence independent of differences in conditioned responding, we recorded single-unit aIC activity in ST and GT rats performing an odor-guided sucrose discrimination task with equivalent approach behavior. At the population level, GT aIC was dominated by task-excited neurons that drove sucrose discrimination, while ST aIC carried a greater proportion of task-inhibited neurons whose suppression carried the dominant discrimination signal, a dissociation specific to the reward epoch. During cue sampling, the balance of excited and inhibited neurons did not differ between phenotypes, but temporal structure diverged: ST cue-excited neurons showed transient CS-onset responses without sustained discrimination, while GT cue-excited neurons maintained sustained CS+/CS-discrimination into the reward epoch. ST cue-period firing predicted post-cue approach latency, with stronger responses associated with slower goal approach, a relationship absent in GT. The majority of optogenetically identified aIC projection neurons targeting basolateral amygdala and nucleus accumbens were cue-inhibited. These findings reveal that individual differences in associative strategy are encoded in the organizational structure of aIC population activity, positioning aIC as a site where motivational strategy is translated into distinct outputs. Significance statement Rats vary in how they respond to reward-predictive cues: some approach the cue itself, while others orient toward the reward location. These strategies reflect individual differences in associative learning poorly understood at the neural level. Using single-unit recording and optogenetic circuit identification, we show that anterior insular cortex encodes reward through opposing organizational principles across these two groups, even when observable behavior is identical. Session-level cue-period activity in sign-tracking rats predicted how slowly they transitioned from the cue to the reward location, a relationship absent in goal-tracking rats. Among optogenetically identified insular projection neurons, the majority showed cue-suppressed activity. These findings identify insular cortex as a site where individual differences in motivational strategy are encoded and transmitted to reward circuits.
Authors: Sara E. Keefer, David A. Martin, Donna J. Calu
Institutions: University of Maryland, Baltimore, Gettysburg College
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7223146162