Distinct signals in medial and lateral VTA dopamine neurons modulate fear extinction at different times
Open Access
- 10 June 2020
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
Abstract
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.Keywords
Funding Information
- National Institutes of Health (T32MH065214)
- New York Stem Cell Foundation
- Army Research Office (W911NF1710554)
- National Institutes of Health (1R01MH106689-01A1)
- McKnight Foundation
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (U19NS104648-01)
- National Institutes of Health (DP2 DA035149-01)
- National Institutes of Health (5R01MH106689-02)
- Pew Charitable Trusts
- National Institutes of Health (F32MH112320-03)
- National Institutes of Health (5R01DA047869)
- New York Stem Cell Foundation (Robertson Investigator)
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