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Distinct signals in medial and lateral VTA dopamine neurons modulate fear extinction at different times

Lili X. Cai, Katherine Pizano, Gregory W. Gundersen, Cameron L. Hayes, Weston T. Fleming, View ORCID ProfileIlana B. Witten
doi: https://doi.org/10.1101/2020.01.14.906024
Lili X. Cai
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08540
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Katherine Pizano
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08540
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Gregory W. Gundersen
Department of Computer Science, Princeton University, Princeton, NJ 08540
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Cameron L. Hayes
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08540
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Weston T. Fleming
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08540
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Ilana B. Witten
Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08540Department of Psychology, Princeton University, Princeton, NJ 08540
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  • ORCID record for Ilana B. Witten
  • For correspondence: iwitten@princeton.edu
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Abstract

Dopamine (DA) neurons are known to encode reward prediction error (RPE), in addition to other signals, such as salience. While RPE is known to support learning, the role of salience in supporting learning remains less clear. To address this, we recorded and manipulated VTA DA neurons in mice during fear extinction, a behavior we observed to generate spatially segregated RPE and salience signals. We applied deep learning to classify mouse freezing behavior, eliminating the need for human scoring. Our fiber photometry recordings showed that DA neurons in medial and lateral VTA have distinct activity profiles during fear extinction: medial VTA activity more closely reflected RPE, while lateral VTA activity more closely reflected a salience-like signal. Optogenetic inhibition of DA neurons in either region slowed fear extinction, with the relevant time period for inhibition differing across regions. Our results indicate that salience-like signals can have similar downstream consequences to RPE-like signals, although with different temporal dependencies.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 15, 2020.
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Distinct signals in medial and lateral VTA dopamine neurons modulate fear extinction at different times
Lili X. Cai, Katherine Pizano, Gregory W. Gundersen, Cameron L. Hayes, Weston T. Fleming, Ilana B. Witten
bioRxiv 2020.01.14.906024; doi: https://doi.org/10.1101/2020.01.14.906024
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Distinct signals in medial and lateral VTA dopamine neurons modulate fear extinction at different times
Lili X. Cai, Katherine Pizano, Gregory W. Gundersen, Cameron L. Hayes, Weston T. Fleming, Ilana B. Witten
bioRxiv 2020.01.14.906024; doi: https://doi.org/10.1101/2020.01.14.906024

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