# Using large scale electrophysiology to study the role of midbrain dopamine neurons underlying motivated behaviors

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $73,336

## Abstract

PROJECT SUMMARY
A core feature of a number of psychiatric illnesses is the disordered estimation of the predictive relationship
between a given cue and an outcome. This failure to appraise and generate appropriate behavioral responses
is true for cues that both are rewarding and aversive. For example, in post-traumatic stress disorders innocuous
stimuli can elicit intense aversive motivational responses even though these were encountered in a safe and
familiar context. On the other hand, in substance use disorders previously drug-paired cues can elicit intense
craving and trigger relapse, despite these cues being encountered in settings where drug use never occurred.
As a result, it is critical to understand the factors and neural systems that support and regulate cue-triggered
motivations in the hope of identifying potential treatments for disorders of motivation. Dopamine neurons within
the ventral tegmental area (VTA) are well known to be responsible for reward-related learning, yet subsets of
VTA dopamine neurons are excited by aversive stimuli which opposes an exclusive role for these neurons in
reward. However, there is limited understanding of how such heterogeneity in VTA dopamine neurons
contributes to the dynamic control of reward and aversion as these are primarily assessed in conditions where
animals learn cue-outcome associations that are rigid and stable which occlude the ability to differentiate the
encoding of value and valence. Here, I propose a novel behavioral approach that dynamically alters the relations
between cues and either rewarding or aversive outcomes on a trial-to-trial basis to understand the contribution
of VTA dopamine neurons to the flexible generation of motivated behaviors. This behavioral approach will allow
me to test whether defined subsets of VTA dopamine neurons encode the long-running learned value versus the
immediate motivational significance of cues that are otherwise ambiguously rewarding or aversive which has
important implications for our understandings of these neurons in health and disease. The primary goals are to
(1) apply a large-scale electrophysiological approach to detail correlates of reward and aversion in projection-
defined VTA dopamine neurons, (2) assess the contribution of distinct VTA dopamine neurons to the flexible
control of reward and aversion, and (3) detail the computations supported by ventral basal ganglia inputs onto
VTA dopamine neurons that make possible the generation of flexible motivated behavior. Collectively the
proposed research provides me extensive training that translates my skills into mice, integrates optogenetics
with large-scale recording approaches, and develops an approach for the recording of neurons in a cell-type and
circuit-defined manner during complex behaviors. Deconstructing the function of VTA dopamine neurons in the
rapid regulation of reward and aversion is a significant step in our understanding of the contributions of these
neurons in psychiatric...

## Key facts

- **NIH application ID:** 10691902
- **Project number:** 5F32MH127792-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Kurt Michael Fraser
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $73,336
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-23

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10691902

## Citation

> US National Institutes of Health, RePORTER application 10691902, Using large scale electrophysiology to study the role of midbrain dopamine neurons underlying motivated behaviors (5F32MH127792-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10691902. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*