# State-dependent regulation of mesolimbic dopamine and ventral striatal neuron activity

> **NIH NIH F32** · J. DAVID GLADSTONE INSTITUTES · 2020 · $64,926

## Abstract

PROJECT SUMMARY/ABSTRACT
 The mesolimbic dopamine system, projecting from the ventral tegmental area (VTA) to the nucleus
accumbens, strongly controls motivation to seek rewards in the environment, including drugs of abuse and
rewards that alter fluid and energy balance. Natural imbalances in internal state that occur over prolonged
timecourses, such as the sensations of hunger and thirst, are critical for expression of motivated behavior.
However, the circuit mechanisms underlying basal ganglia circuit activity during different homeostatic states
remains unclear. With the recent development of single neuron resolution imaging tools, optical calcium
sensors, and optical neurotransmitter sensors, dopamine activity in the ventral midbrain as well as in the
ventral striatum can be easily measured. The goal of this work is to determine how selective activity
patterns in VTA dopamine neurons change during different internal states and how those changes in
activity drive differences in firing patterns of medium spiny output neurons in the nucleus accumbens
during action selection. To address this, I will use a freely-moving cued approach tone discrimination task in
which food- and water-predictive cues are randomly delivered while performing single-neuron resolution
imaging of dopamine neuron calcium activity using a head-mounted mini-microscope. I hypothesize that
dopamine neurons will preferentially respond to the deprived cue and reward while also weakly responding to
the non-deprived stimuli, and that this will depend on activity in upstream brain regions required for hunger and
thirst expression. Further, I hypothesize that this difference in dopamine cell activity will lead to a bidirectional
modulation of striatal output activity that tracks local dopamine release and deprivation-evoked action
selection. This work will build on prior research done on striatal circuits in our lab as well as on interoceptive
circuitry in other labs at our institution. I will learn skills in in vivo recording techniques as well as behavioral
design and data analysis. With this project, I hope to further understand fundamental pre- and post-synaptic
circuit mechanisms underlying dopaminergic activity in state-dependent motivation.

## Key facts

- **NIH application ID:** 10068231
- **Project number:** 1F32DA052283-01
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Aphroditi Mamaligas
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10068231

## Citation

> US National Institutes of Health, RePORTER application 10068231, State-dependent regulation of mesolimbic dopamine and ventral striatal neuron activity (1F32DA052283-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10068231. Licensed CC0.

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