Cholinergic interneurons in the nucleus accumbens regulate the initiation of natural reward approach

Brown, S. O.; Durand-de Cuttoli, R.; Mahboob, M. A.; Markopoulou, E.; Ibanez-Tallon, I.; Ables, J. L.

doi:10.64898/2026.09.23.753195

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bioRxiv · 10.64898/2026.09.23.753195

Cholinergic interneurons in the nucleus accumbens regulate the initiation of natural reward approach

Brown, S. O.·Durand-de Cuttoli, R.·Mahboob, M. A.·Markopoulou, E.·Ibanez-Tallon, I.·Ables, J. L.

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Abstract

Despite their established role in motivated behavior, how nucleus accumbens (NAc) cholinergic interneurons (CINs) contribute to natural reward seeking remains unclear. Here, we report that NAc CINs are key modulators of the approach phase of reward pursuit. Using in vivo fiber photometry in Chat-ires-Cre mice, we show that NAc CINs are robustly activated during the approach towards several salient stimuli including food, a social target, and a familiar object. We also provide evidence that this activation is potentially driven by olfactory cues. Disrupting NAc CIN function via targeted expression of a membrane-tethered toxin results in a delayed approach towards both food and a social target, but no alterations in object investigation, general locomotion or anxiety-related measures. Together, these findings identify NAc CINs as regulators of the initiation of natural reward approach and suggest that they link sensory information with onset of motivated action.

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Brown, S. O., Durand-de Cuttoli, R., Mahboob, M. A., Markopoulou, E., Ibanez-Tallon, I., Ables, J. L.. 2026-09-24. Cholinergic interneurons in the nucleus accumbens regulate the initiation of natural reward approach. https://doi.org/10.64898/2026.09.23.753195

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