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Published March 24, 2021 | Published + Submitted
Journal Article Open

Dorsal Raphe Dopamine Neurons Signal Motivational Salience Dependent on Internal State, Expectation, and Behavioral Context


The ability to recognize motivationally salient events and respond to them adaptively is critical for survival. Here we tested whether dopamine (DA) neurons in the dorsal raphe nucleus (DRN) contribute to this process. Population recordings of DRN^(DA) neurons during associative learning tasks showed that their activity dynamically tracks salience, developing excitation to both reward- and punishment-paired cues. The DRNDA response to reward-predicting cues was diminished after satiety, suggesting modulation by internal states. DRN^(DA) activity was also greater for unexpected outcomes than for expected outcomes. Two-photon imaging of DRN^(DA) neurons demonstrated that the majority of individual neurons developed activation to reward predicting cues but not to punishment-predicting cues, which was surprising and qualitatively distinct from the population results. Head-fixation during fear learning abolished the neural response to aversive cues, indicating modulation by behavioral context. Overall, these results suggest that DRN^(DA) neurons encode motivational salience, dependent on internal and external factors.

Additional Information

© 2021 the authors. Received Oct. 19, 2020; revised Jan. 19, 2021; accepted Jan. 26, 2021. This work was supported by the National Institutes of Health (NIH) Director's New Innovator Grant IDP20D091182-01, Presidential Early Career Award for Scientists and Engineers, the NIH/National Institute on Aging Grant 1R01AG047664-01, the NIH Grant BRAIN 1U01NS090577, Heritage Medical Research Institute, Chen Institute (V.G.), Beckman Institute (V.G. and D.A.W.), Tianqiao & Chrissy Chen Institute Chen Graduate Fellowship (X.C.), Colvin Divisional Fellowship at Caltech (A.K.), and the Children's Tumor Foundation Young Investigator Award 2016-01-00 (to J.E.R.). We thank the entire Gradinaru lab for critical feedback. Author contributions: J.R.C. and V.G. designed research; J.R.C., X.C., A.K., and J.E.R. performed research; A. K. and D.A.W. contributed unpublished reagents/analytic tools; J.R.C. and X.C. analyzed data; J.R.C. and V.G. wrote the paper. The authors declare no competing financial interests.

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Published - 2645.full.pdf

Submitted - 2020.07.27.222729v1.full.pdf


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August 22, 2023
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