# The effects of context and physiological state on mesolimbic encoding of reward

> **NIH NIH F32** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $69,810

## Abstract

Project title: The effects of context and physiological state on mesolimbic encoding of reward
PROJECT SUMMARY/ABSTRACT
The encoding of reward is a complex process that is regulated by a variety of factors that extend beyond
primary stimulus features to include interactions between contextual and discrete cues in the environment and
changes to physiological state. In general, the encoding of reward and subsequent goal-oriented behaviors are
often adaptive and essential for survival. However, humans world-wide are often bombarded with
environmental contextual cues that can trigger maladaptive reward-seeking behaviors that are rampant in
prominent health issues like obesity and drug addiction. While many have studied the mesolimbic system
under the lens of both adaptive and maladaptive goal-directed behaviors, surprisingly little is known about the
contribution of contextual cues in modulating the mesolimbic system. Moreover, the functions of the
mesolimbic system are powerfully modulated by physiological state and can influence how mesolimbic phasic
dopamine responses encode particular outcomes (e.g. food, water, and drugs of abuse). [[Thus, a major
aim of this proposal is to delineate the neural substrates that integrate information about
contextual cues, discrete cues, and physiological state, which subsequently guide goal-
oriented behaviors. VTA-NAc phasic dopamine activity has been strongly implicated in goal-directed
behaviors and is robustly influenced by physiological state. In Aim I, we utilize in vivo fiber photometry in
awake, behaving animals to generate real-time recordings from VTA dopamine neurons while animals learn to
associate water availability with discrete cues. We then examine the thirst neurons of the subfornical organ
(SFO) as a primary neural substrate that relays physiological state information to VTA dopamine neurons
using fiber photometry and chemogenetic manipulations. Based on previous work and pilot data, we
anticipate that the SFO is necessary and sufficient for the modulation of water-cue evoked VTA phasic
dopamine activity. We will also determine the multi-synaptic path by which the SFO communicates with the
VTA. In Aim II, we consider VTA phasic dopamine signaling as an integrator of both physiological state and
contextual cues that is in part modulated by input from the ventral hippocampus (vHP). Here we use fiber
photometry in VTA dopamine neurons in conjunction with vHP chemogenetics during a novel behavioral task
where animals learn to associate water availability with contexts paired with either water-deprivation or water-
satiation. When water-satiated, we expect water-deprivation contexts to augment water-cue evoked VTA
phasic dopamine signaling and that this response is dependent on vHP mediated context processing. Taken
together, the novel findings from these studies will allow for a greater understanding of how goal-directed
behaviors are acquired and expressed within the brain and provide important mec...

## Key facts

- **NIH application ID:** 9991610
- **Project number:** 5F32DA047052-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Ted Hsu
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $69,810
- **Award type:** 5
- **Project period:** 2019-06-20 → 2022-06-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991610

## Citation

> US National Institutes of Health, RePORTER application 9991610, The effects of context and physiological state on mesolimbic encoding of reward (5F32DA047052-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9991610. Licensed CC0.

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