# Regulation of central circadian rhythms by dopamine

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $318,460

## Abstract

Project Summary/Abstract: Our circadian clocks have evolved to synchronize behavioral and physiological
activities to a specific time of the day in order to optimize survival. Although Darwinian pressures have declined
for humans, many of the emergent stresses of modern society burdens our ancient circuitry governing
circadian synchrony. As such, new pathologies are emerging including mental, cardiovascular, metabolic
disorders and cancer. The synchronization process of biological rhythms, termed entrainment, requires
environmental cues (zeitgebers) that are able to reset the molecular clock machinery. For mammals, the most
dominant daily zeitgeber is light. During photoentrainment, the ambient light levels that are detected by
photoreceptors are conveyed to the central circadian clock located in the suprachiasmatic nucleus (SCN) of
the hypothalamus to permit synchrony to day/night cycles. However, other cues such as availability of food,
social interactions or physical exercise also influence the phase of the SCN. Why have multiple modes of
entrainment evolved? Perhaps the most parsimonious explanation for the evolution of these circuits is that they
inform the central circadian clock of salient events such as availability of food or a mate during a temporally
distinct niche. These types of behaviors are thought to be regulated by neural circuits associated with
dopamine (DA). Existence of SCN independent oscillators that are closely associated with DA further highlights
the importance of this neurotransmitter in establishment of an integrated and well informed biological timing
process. In this proposal, we hypothesize that increased DA signaling in the SCN allows the central oscillator
to enter a more “entrainment susceptible” state where new cues are able to adjust the circadian clock more
readily. To address this idea we provide preliminary evidence and propose two specific aims. In Aim 1, we
examine the existence of a functional connection between a select group of DA producing cells and the
recipients of these connections in the SCN, which express the DA receptor Drd1. To this end, we propose to
measure DA release and ensuing changes in SCN-neuron activity by using pharmacological methods and
actuator systems that elevate or inhibit the activity of a genetically defined group of DA-neurons. The functional
mapping strategy outlined in this aim provides the framework to delineate this previously undefined neural
circuit in circadian entrainment. In Aim 2, we seek to define the molecular mechanism(s) of how DA-induced
activation of Drd1-expressing neurons in the SCN modulates circadian entrainment. To accomplish this, we will
first confirm that elevated or reduced activity of Drd1-expressing SCN neurons modulates entrainment.
Subsequently, we determine whether DA release in the SCN hastens circadian clock entrainment and whether
Drd1 expression in the SCN is necessary and/or sufficient for this response. The findings and proposed
experiments ...

## Key facts

- **NIH application ID:** 10004681
- **Project number:** 5R01GM121937-05
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Ali Guler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $318,460
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004681

## Citation

> US National Institutes of Health, RePORTER application 10004681, Regulation of central circadian rhythms by dopamine (5R01GM121937-05). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10004681. Licensed CC0.

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