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, Sebastian Holt, Julia M. Cox, Ilana B. Witten

Research output: Contribution to journalArticle

Abstract

Dopamine (DA) neurons are 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.

Original languageEnglish (US)
Article numbere54936
Pages (from-to)1-23
Number of pages23
JournaleLife
Volume9
DOIs
StatePublished - Jun 2020

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Distinct signals in medial and lateral VTA dopamine neurons modulate fear extinction at different times'. Together they form a unique fingerprint.

  • Cite this

    Cai, L. X., Pizano, K., Gundersen, G. W., Hayes, C. L., Fleming, W. T., Holt, S., Cox, J. M., & Witten, I. B. (2020). Distinct signals in medial and lateral VTA dopamine neurons modulate fear extinction at different times. eLife, 9, 1-23. [e54936]. https://doi.org/10.7554/eLife.54936