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

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  • Lili X Cai
    Princeton Neuroscience Institute, Princeton University, Princeton, United States
  • Katherine Pizano
    Princeton Neuroscience Institute, Princeton University, Princeton, United States
  • Gregory W Gundersen
    Department of Computer Science, Princeton University, Princeton, United States
  • Cameron L Hayes
    Princeton Neuroscience Institute, Princeton University, Princeton, United States
  • Weston T Fleming
    Princeton Neuroscience Institute, Princeton University, Princeton, United States
  • Sebastian Holt
    Princeton Neuroscience Institute, Princeton University, Princeton, United States
  • Julia M Cox
    Princeton Neuroscience Institute, Princeton University, Princeton, United States
  • Ilana B Witten
    Princeton Neuroscience Institute, Princeton University, Princeton, United States

Description

<jats:p>Dopamine (DA) neurons are thought 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 learning remains less clear. To address this, we recorded and manipulated VTA DA neurons in mice during fear extinction. We applied deep learning to classify mouse freezing behavior, eliminating the need for human scoring. Our fiber photometry recordings showed 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 salience-like signals can have similar downstream consequences to RPE-like signals, although with different temporal dependencies.</jats:p>

Journal

  • eLife

    eLife 9 2020-06-10

    eLife Sciences Publications, Ltd

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