# Probing the neural representation of information acquired under the influence of midbrain dopamine transients

> **NIH NIH FI2** · U.S. NATIONAL INSTITUTE ON DRUG ABUSE · 2020 · —

## Abstract

Project Summary
Learning associations between environmental stimuli and the reinforcing events they predict is necessary for
survival. Animals and humans use these stimuli to learn where to acquire food, how to avoid predators, or
where to find a mate. Learning associations between stimuli that do not predict appetitive or aversive events is
equally important. While dopamine signaling was previously thought to only contribute to learning when there
are changes in the value of a stimulus, recent work has found a role for dopamine neuron firing in forming
more complex cognitive representations between neutral stimuli. Modern optogenetic techniques have allowed
us to artificially stimulate dopamine neuron activity during a situation in which cues are present but normally
“blocked” from producing learning under naturalistic conditions. The learning that results from this stimulation
cannot be easily accounted for by reward prediction errors that only contain scalar quantities reflecting the
value of future events, which dopamine was thought to be restricted to, and instead suggests dopamine drives
the acquisition of associations between sensory events independent of value. While this artificial stimulation
produces behavior that appears as if animals had learned normally, it is unknown how close the neural engram
acquired under these conditions is to that learned naturally. Thus, the first goal of this proposal is to measure
neural responses to stimuli that were learned under naturalistic versus artificially stimulated conditions.
Single unit recording has yielded transformative information in the study of attention, visual processing, and
learning, among others. While single unit recording unequivocally represents the output of a neuron, more
recent tools such as calcium imaging that use genetically encoded calcium indicators that fluoresce in
response to intracellular calcium are increasingly being used. Fluorescence is used to “infer” neural activity that
may or may not be the same information recorded with a microelectrode. Critically, single-photon calcium
signals have never been directly compared to electrophysiological signals in awake, behaving animals. I will
subject separate groups of rats to the same behaviors while recording with calcium imaging or
microelectrodes. The second goal of this project is to directly compare these two signals.
I will assess real-time ensemble activity of the orbitofrontal cortex, a cortical target of the dopamine system that
supports various forms of associative learning, during responding to normally versus artificially conditioned
stimuli. I will test how closely the neural responses to artificially learned cues correspond to similar cues that
have been learned about naturally. I will directly compare electrophysiological and single-photon calcium data.
These experiments will pull from my strong background in learning theory and in-vivo calcium imaging I
acquired in graduate school. Importantly, I will use th...

## Key facts

- **NIH application ID:** 10025810
- **Project number:** 1FI2GM133534-01A1
- **Recipient organization:** U.S. NATIONAL INSTITUTE ON DRUG ABUSE
- **Principal Investigator:** Evan Hart
- **Activity code:** FI2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025810

## Citation

> US National Institutes of Health, RePORTER application 10025810, Probing the neural representation of information acquired under the influence of midbrain dopamine transients (1FI2GM133534-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10025810. Licensed CC0.

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