# Circuit mechanisms of functional diversity of dopamine neurons during complex behavior

> **NIH NIH K99** · PRINCETON UNIVERSITY · 2020 · $118,941

## Abstract

Project Abstract
 Dopamine is a neurotransmitter critical to normal brain function and has been implicated in a diverse
array of brain disorders, including schizophrenia, depression, ADHD, addiction and others. The specific etiology
of dopamine dysfunction in the different disorders has in turn been associated with distinct behavioral deficits.
Thus, the clinical literature has ascribed to dopamine a wide array of behavioral and cognitive roles, including
working memory, attention, motivation, learning, and many more. Contrary to this view, in the neurobiological
literature, it has been a long-standing consensus that dopamine has a limited behavioral role: the processing of
a reward prediction error signal. Thus, there is a fundamental gap between the clinical and neurobiological fields
which must be bridged in order to understand the function of the dopamine system and to enable the
development of improved therapeutics for the treatment of the different types of dopamine dysfunction.
 Studies showing that dopamine neurons comprise a functionally homogenous population whose activity
could be well explained as a reward prediction error signal were mostly performed using simple cue-reward
association behaviors. Recently I showed that during complex behavior, dopamine neurons divide into distinct,
anatomically organized, functional subpopulations that mediate different aspects of the behavior. This diversity
of function of the dopamine population could potentially underlie the diversity of behavioral roles attributed to
dopamine in the clinical literature and suggests that dopamine neurons may flexibly encode a diverse array of
behavioral variables via distinct functional subpopulations that emerge in response to behavioral demands.
 The goal of this project is to study the neural basis of the newly discovered diversity in dopamine function,
and the precise behavioral role of the different functional dopaminergic subpopulations. In the mentored stage
(K99) I will combine the use of deep-brain two-photon imaging with an array of precise behavioral tasks in virtual-
reality to determine the relationship between behavioral complexity and the degree of functional diversity in the
population of dopamine neurons (Aim 1). I will then leverage the power of two-photon imaging for recording the
same neurons across days in order to study whether the specialized dopaminergic subpopulations generalize
their functional role across task conditions (Aim 2, K99 phase). In this stage I will also learn the use of subregion-
specific optogenetic techniques, which will allow me to probe the causal role of these subpopulations in behavior
(Aim 2, R00 phase). Finally, I will uncover the neural basis of the functional diversity of dopamine neurons by
recording and causally manipulating specific inputs to dopamine neurons during complex behavior (Aim 3, R00
phase). By using state-of-the art neurophysiological tools and expanding the study of dopamine to complex
behavior, th...

## Key facts

- **NIH application ID:** 9953477
- **Project number:** 1K99MH122657-01
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Ben Engelhard
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $118,941
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953477

## Citation

> US National Institutes of Health, RePORTER application 9953477, Circuit mechanisms of functional diversity of dopamine neurons during complex behavior (1K99MH122657-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9953477. Licensed CC0.

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