Dopamine biases anterior insula representations toward negative valence through D1 receptors
Year: 2026
Type: article
Abstract: Dopamine is widely implicated in motivational and emotional states, yet how it contributes to the cortical encoding of negative valence remains poorly understood. The anterior insular cortex (aIC) is critically involved in aversive processing and anxiety, but the neuromodulatory mechanisms shaping these representations are unknown. Here, we investigated dopamine dynamics and D1 receptor-dependent modulation of valence representations in the mouse anterior insular cortex. Using in vivo fiber photometry, we found that following aversive foot-shocks, dopamine signals increased in the anterior, but not posterior insula, preferentially at D1+ over D2+ neurons. Dopamine responses at D1+ neurons scaled with individual anxiety-like behavior, and optogenetic activation of anterior insula D1+ neurons was sufficient to drive avoidance. Dopamine signals also discriminated taste valence, decreasing during consumption of appetitive sucrose and increasing following aversive quinine consumption. Finally, systemic D1 receptor activation selectively altered anterior insula taste representations: it reduced quinine-evoked responses at the single-unit level while weakening the population representation of sucrose, resulting in reduced separability between appetitive and aversive taste representations. Together, these findings identify a D1-dependent dopaminergic signal in the anterior insular cortex associated with negative valence and anxiety, and reveal that systemic D1 activation reorganizes cortical population activity toward an aversive-like state. Thus, our study reveals a previously unrecognized role for cortical dopamine in shaping negative-valence representations and provides a mechanistic link between dopamine, insular valence processing, and anxiety.
Institutions: Université de Bordeaux, Inserm, Peking University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7213925709