# Restoration and Further Assessment of the Actor-Critic Circuit and Connected Areas After Cocaine Self-Administration

> **NIH NIH R01** · UNIV OF MARYLAND, COLLEGE PARK · 2021 · $353,410

## Abstract

PROJECT SUMMARY
Reward-guided decision-making and impulse control are disrupted after chronic cocaine use. These changes
have been attributed to altered function in brain circuits critical for computations of reward predictions and
action policies. `Reward prediction' signals reflect the reward the animal expects to receive as a result of
behavior, thus reflecting goals associated with decisions. `Action policies' are rules that govern behavior that at
triggered by external stimuli or context, and are thought to underlie habits. Both reward predictions and action
policies are modified when there are violations in predictions known as `reward prediction errors'. `Signed'
reward prediction errors reflect the valence associated with an error, strengthening or weakening the
associability between cues and outcomes/responses. `Unsigned' prediction errors reflect the surprise induced
by errors which lead to increases in attention so that learning can occur. We have uncovered neural correlates
of these constructs and the relationship between them by recording from multiple brain areas as rats perform
an odor guided decision-making task in which we unexpectedly varied the delay to and size of reward across
several trial blocks. We have shown that nucleus accumbens core (NAc) encodes reward predictions, firing
strongly for cues that predict more valued reward, whereas firing in dorsal lateral striatum (DLS) is highly
associative, encoding action policies such as stimulus-response associations and contextual bias signals (e.g.,
in this context bias choices to the right). We have also shown that midbrain dopamine (DA) neurons increase
firing to unexpected reward and decrease firing to unexpected reward omission. During learning these signed
prediction errors transfer to cues, with cues predicting more valued reward eliciting stronger firing. Unlike firing
of DA neurons, our work has shown that firing in anterior cingulate cortex (ACC) better reflects an integrated
unsigned reward prediction error signal, increasing during unexpected up- and down-shifts in value at the time
of the error and during cue sampling on subsequent trials. This work suggests a model by which DA reward
prediction errors modify reward prediction signals in NAc and action policy signals in DLS, while ACC
increases attention toward stimuli after violations in reward prediction (signaled by DA) so that learning can
occur. Cocaine exposure impairs reward prediction signals and prediction error signals in NAc and DA
neurons, while increasing the prevalence of contextual action policies in DLS. In Aim 1 we propose to restore
the cocaine induced imbalance of processing between NAc and DLS by repairing DA signals via optogenetics.
In Aim 2 we will determine if attention and error correlates in ACC are altered after cocaine exposure. Finally,
in Aim 3, we will determine how ACC and DA neurons interact during the computation of errors and the
development of cue selectivity. By performing these e...

## Key facts

- **NIH application ID:** 10087906
- **Project number:** 5R01DA031695-10
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** MATTHEW R ROESCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $353,410
- **Award type:** 5
- **Project period:** 2011-07-01 → 2023-04-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087906

## Citation

> US National Institutes of Health, RePORTER application 10087906, Restoration and Further Assessment of the Actor-Critic Circuit and Connected Areas After Cocaine Self-Administration (5R01DA031695-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10087906. Licensed CC0.

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