# Network Properties of Circadian Clock Modulation and Entrainment

> **NIH NIH R01** · ADVANCED SCIENCE RESEARCH CENTER · 2020 · $339,683

## Abstract

Our circadian clocks orchestrate endogenous biological rhythms in physiology, metabolism, and behavior that
must be adjusted every day to maintain synchrony with the environment and produce optimally timed rhythmic
outputs. This daily adjustment, known as entrainment, is achieved through a sensitivity of the brain's central
clock neuron network to both external and internal time cues. Postindustrial society has significantly reduced the
reliability of the cues that our circadian system uses for entrainment. This modern challenge to our clocks has
wide-spread negative health consequences. The complexity of the brain's clock center is a significant barrier to
a comprehensive understanding of the daily adjustment of the circadian system. Understanding the network
properties of circadian timekeeping in the brain and the ways in which time cues impinge upon clock centers is
critical if we are to address the significantly negative effects of circadian misalignment and dysfunction. The
broad goal of this competing renewal application is a comprehensive understanding of the network properties of
circadian timekeeping and entrainment in Drosophila melanogaster, whose circadian system features highly
conserved molecular, anatomical, and physiological features that it shares with mammalian clock networks.
Within this well-defined clock center, we will investigate how highly conserved external and internal time cues
produce network-wide clock modulation and control sleep. The goals of our three specific aims are to elucidate:
1) the mechanistic basis of cholinergic and GABAergic inputs into the clock neuron network and the roles they
play in sleep control and circadian timekeeping and entrainment, 2) the neurophysiological mechanisms by which
the various clock neuron classes of the clock network modulate one another to produce coherent circadian
rhythms, and 3) the anatomical and neurophysiological basis of the network integration of light and temperature
cues from peripheral sensory receptors. The unifying goal of this proposal is to advance our understanding of
circadian timekeeping and entrainment in the brain. The results of this work will ultimately inform the
development and implementation of interventions designed to alleviate the significantly adverse metabolic and
psychological effects of circadian dysfunction in the modern world.

## Key facts

- **NIH application ID:** 9828602
- **Project number:** 5R01NS077933-09
- **Recipient organization:** ADVANCED SCIENCE RESEARCH CENTER
- **Principal Investigator:** ORIE T SHAFER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $339,683
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828602

## Citation

> US National Institutes of Health, RePORTER application 9828602, Network Properties of Circadian Clock Modulation and Entrainment (5R01NS077933-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9828602. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*