# Task Representations in Ventral Tegmental Area Dopamine Neurons across Shifts in Behavioral Strategy and Reward Expectation

> **NIH NIH F32** · PRINCETON UNIVERSITY · 2024 · $76,756

## Abstract

ABSTRACT
Optimal decision-making requires a delicate balance of stability and flexibility. On the one hand, stability is
required to exploit learned contingencies between environmental features, instrumental actions, and goals. On
the other, flexibility is required for the acquisition of a new behavioral strategy when the contingencies change.
Dopamine (DA) neurons of the ventral tegmental area (VTA) have been implicated as important regulators of
this balance. Conditions associated with DA dysfunction–most notably schizophrenia, Parkinson’s, and
Huntington’s disease–profoundly disrupt performance on tasks requiring behavioral flexibility, such as the
Wisconsin Card Sorting Test, typically by increasing “perseverative” responses that track a previously learned
feature that is no longer relevant. Numerous animal studies have also directly implicated DA in the capacity to
shift strategies, using pharmacological interventions, DA depletion, and microdialysis in important projection
targets of VTADA neurons. Moreover, VTADA stimulation can promote either the maintenance or reorganization
of behavioral strategy depending on whether it is timed to mimic tonic or phasic modes of firing. However,
little is known about the endogenous neural activity patterns that underlie the acquisition of a new strategy–in
part, because its anatomical location deep within the brain has kept the VTA inaccessible to large-scale
recording during behavior. We have developed a decision making paradigm for mice that requires a strategy
shift and can be performed under a two-photon microscope, allowing the use of state-of-the-art deep-brain
imaging techniques to simultaneously monitor VTADA activity at cellular resolution. In this task, subjects
navigate a T-maze within a virtual reality environment. The reward location is determined by one of two rules:
a sensory rule guided by visuospatial cues, or an alternation rule guided by the previous choice. After initial
training on one rule, subjects are challenged with a rule shift that enforces the acquisition of a new strategy.
The recent discovery of heterogeneous task-feature representations within the VTADA population–a finding that
contradicts the standard view that VTADA broadcasts a global reward prediction error signal–has inspired us to
use this paradigm to test an intriguing hypothesis: that the RPE is represented in multiple feature-specific
components–rather than as a global signal–and that subsets of the VTADA population track specific features
based on their relevance to the current task strategy. Thus, the research plan outlined in this proposal will
allow the first characterization of endogenous VTADA activity during a shift in behavioral strategy, and may help
to clarify the link between DA and theories of reinforcement learning. The results are expected to have broad
relevance to decision-making, and may uncover specific mechanisms that link dopamine dysfunction to deficits
in flexibility.

## Key facts

- **NIH application ID:** 10909851
- **Project number:** 5F32MH131325-02
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Michael James Siniscalchi
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $76,756
- **Award type:** 5
- **Project period:** 2023-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909851

## Citation

> US National Institutes of Health, RePORTER application 10909851, Task Representations in Ventral Tegmental Area Dopamine Neurons across Shifts in Behavioral Strategy and Reward Expectation (5F32MH131325-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10909851. Licensed CC0.

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