# Neural circuit regulation of ramping activity in dopamine neurons

> **NIH NIH R01** · CORNELL UNIVERSITY · 2024 · $1

## Abstract

Project Summary
Ventral striatal dopamine progressively rises as rodents navigate toward spatially distant rewards, a surprising
recent finding that was not anticipated by temporal difference learning models of dopamine function. Ramping
dopamine release in the ventral striatum reflects the value and proximity of goals, scaling by the value of the
reward and stretching or compressing in different environments to span the distance between start and goal
locations. Activity in ventral tegmental area (VTA) dopamine neurons also ramps up as animals approach
goals, but the strength and persistence of ramping activity in dopamine neurons depends on both the use of an
internal model of goal proximity and on the amount of task experience. Ramping activity in dopamine neurons
appears immediately when naïve mice run toward newly-discovered rewards in spatial environments, and
ramps gradually fade away over several days of training if sensory information about reward proximity is
available. When an internal representation of progress toward the goal is required, however, robust ramping
activity in dopamine neurons persists indefinitely. These findings suggest the hypothesis that ramping activity
in VTA dopamine neurons depends on the use of brain regions that represent an internal model of the
environment and current progress toward goals. We propose to test this overarching hypothesis by addressing
the following specific aims: 1) Test the hypothesis that neural activity in the ventral hippocampus contributes to
ramping activity in midbrain dopamine neurons. 2) Compare the evolution of ramping activity in VTA dopamine
neurons with the evolution of ramping dopamine release in the ventral striatum. 3) Characterize neural activity
in VTA GABA neurons during spatial and non-spatial navigation to rewards. Understanding the neural
mechanisms that underlie ramping activity in dopamine neurons will have relevance for the neural basis of
cognitive control, goal-directed behavior, perseverance, and spatial learning. Our findings will provide valuable
information relevant for mental disorders associated with dysfunction in these abilities including attention deficit
hyperactivity disorder, obsessive compulsive disorder, depression, and addiction.

## Key facts

- **NIH application ID:** 10795956
- **Project number:** 5R01DA055075-03
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Melissa Rhoads Warden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2022-05-01 → 2024-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795956

## Citation

> US National Institutes of Health, RePORTER application 10795956, Neural circuit regulation of ramping activity in dopamine neurons (5R01DA055075-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10795956. Licensed CC0.

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