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

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.

A Comparison of Dopaminergic and Cholinergic Populations Reveals Unique Contributions of VTA Dopamine Neurons to Short-Term Memory

“…Another issue left unaddressed in the present study is the potential functional difference in distinct VTA-DA subpopulations. There is increased appreciation that VTA-DA neurons have heterogeneous and non-canonical signals during certain tasks (Bromberg-Martin et al, 2010;Cai et al, 2020;Coddington and Dudman, 2018;Engelhard et al, 2019;Howe and Dombeck, 2016;Howe et al, 2013;Lee et al, 2019;Lerner et al, 2015;Menegas et al, 2018;Parker et al, 2016;da Silva et al, 2018). For example, there might be a population of neurons with elevated activity during the delay period, and it is specifically those neurons that are contributing causally to short-term memory performance, but not the population as a whole.…”

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

“…Custom MATLAB software was developed for parts (1 - 2), and custom Python software was developed for parts (3 - 5). Code for all steps is available on GitHub: https://github.com/neurocaience/deepfreeze/ ( Cai et al, 2020 ; copy archived at https://github.com/elifesciences-publications/deepfreeze ).…”

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

“…All mice underwent identical surgery, water restriction, and head-fixation habituation procedures before being randomly assigned to either the freely-moving or the head-fixed group. The fear learning task was slightly different from the ones described above and was adapted from previous studies (Groessl et al, 2018;Cai et al, 2020). White noise (20 seconds) was used as the CS.…”