Temporal Dynamics of Nucleus Accumbens Neurons in Male Mice During Reward Seeking

Schall, T. A.; Li, K.-l.; Qi, X.; Lee, B. T.; Wright, W. J.; Alpaugh, E. E.; Zhao, R. J.; Liu, J.; Li, Q.; Zeng, B.; Wang, L.; Huang, Y. H.; Schlueter, O.; Nestler, E. J.; Nieh, E. H.; Dong, Y.

doi:10.1101/2024.09.27.615291

bioRxiv · 10.1101/2024.09.27.615291

Temporal Dynamics of Nucleus Accumbens Neurons in Male Mice During Reward Seeking

Schall, T. A.·Li, K.-l.·Qi, X.·Lee, B. T.·Wright, W. J.·Alpaugh, E. E.·Zhao, R. J.·Liu, J.·Li, Q.·Zeng, B.·Wang, L.·Huang, Y. H.·Schlueter, O.·Nestler, E. J.·Nieh, E. H.·Dong, Y.

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Abstract

The nucleus accumbens (NAc) regulates reward-motivated behavior, but the temporal dynamics of NAc neurons that enable "free-willed" animals to obtain rewards remain elusive. Here, we recorded Ca2+ activity from individual NAc neurons when mice performed self-paced lever-presses for sucrose. NAc neurons exhibited three temporally-sequenced clusters, defined by times at which they exhibited increased Ca2+ activity: approximately 0, -2.5 or -5 sec relative to the lever-pressing. Dopamine D1 receptor (D1)-expressing neurons and D2-neurons formed the majority of the -5-sec versus -2.5-sec clusters, respectively, while both neuronal subtypes were represented in the 0-sec cluster. We found that pre-press activity patterns of D1- or D2-neurons could predict subsequent lever-presses. Inhibiting D1-neurons at -5 sec or D2-neurons at -2.5 sec, but not at other timepoints, reduced sucrose-motivated lever-pressing. We propose that the time-specific activity of D1- and D2-neurons mediate key temporal features of the NAc through which reward motivation initiates reward-seeking behavior.

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Schall, T. A., Li, K.-l., Qi, X., Lee, B. T., Wright, W. J., Alpaugh, E. E., Zhao, R. J., Liu, J., Li, Q., Zeng, B., Wang, L., Huang, Y. H., Schlueter, O., Nestler, E. J., Nieh, E. H., Dong, Y.. 2024-09-30. Temporal Dynamics of Nucleus Accumbens Neurons in Male Mice During Reward Seeking. https://doi.org/10.1101/2024.09.27.615291

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