# Network Properties of Circadian Clock Modulation and Entrainment

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2024 · $375,165

## Abstract

Abstract
Circadian clocks orchestrate endogenous daily rhythms in physiology, metabolism, and behavior that
must be adjusted (i.e., entrained) to environmental cycles to maintain properly timed outputs. Post-
industrial environments have significantly reduced the reliability of the time cues that the circadian system
relies upon for entrainment and this has had widespread and negative consequences for human health.
Understanding the network properties of circadian timekeeping in the brain and the ways in which time
cues impinge upon it is required if we are to address the adverse effects of circadian misalignment and
dysfunction. The complexity of the brain’s clock center is a significant barrier to our understanding of the
daily adjustment of the circadian system. Work in relatively “simple” clock neuron networks can therefore
enrich and inform our understanding of circadian timekeeping and entrainment in the mammalian brain.
The goal of this competing renewal application is to continue a productive and impactful research program
on the network properties of circadian timekeeping and entrainment in Drosophila melanogaster, which,
despite its relative simplicity, shares molecular, anatomical, and physiological features that are
remarkably similar to those of mammalian clock networks. Within the fly’s clock neuron network, we will
determine how endogenous circadian timekeeping is supported by the network structure of the of the
brain’s clock center and how specific neural pathways and neurotransmitters mediate entrainment to
environmental cycles. The goals of our three specific aims are to elucidate: 1) the nature and timekeeping
functions of the synaptic and modulatory connections of the circadian clock neuron network, 2.) how the
CCNN integrates light input to entrain circadian rhythms, and 3) how neurons that do not themselves
express molecular clocks participate in the clock neuron network to support endogenous timekeeping.
The unifying goal of this research program is to advance our understanding of circadian timekeeping and
entrainment in the brain. The results of this work will inform future interventions for the alleviation of the
adverse health effects of circadian dysfunction in post-industrial environments.

## Key facts

- **NIH application ID:** 11136100
- **Project number:** 7R01NS077933-13
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** ORIE T SHAFER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $375,165
- **Award type:** 7
- **Project period:** 2012-12-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11136100

## Citation

> US National Institutes of Health, RePORTER application 11136100, Network Properties of Circadian Clock Modulation and Entrainment (7R01NS077933-13). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11136100. Licensed CC0.

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