# Micro-Anatomical Mechanisms of Neuronal Circadian Timekeeping, Output, and Entrainment

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2024 · $259,352

## Abstract

Abstract
Circadian clocks orchestrate myriad molecular, physiological, and behavioral processes to insure internal
temporal order and optimal daily timing. In animals, the master clock resides deep within the brain where it relies
on complex neural networks to ensure a robust internal sense of time that can readily synchronize with 24-h
environmental cycle. There is growing consensus that the operation of our master circadian clock under modern
light and social environments contributes significantly to a troubling array of health challenges. Understanding
the neural mechanisms underlying circadian timekeeping and the synchronization of the master pacemaker with
environmental cycles (i.e., entrainment) is therefore critical. A significant barrier to our understanding of the
central circadian clock is the complexity of its constituent neural networks, a complexity compounded by the fact
that clock-containing neurons employ multiple neurochemical signals that act via distinct signaling mechanisms.
Critical clock neurons in both mammals and insects express multiple transmitters – including peptide co-
transmitters - some of which function as local signals across defined synapses while others act as diffusible
signals that act over large distances. Peptide co-release, though a common feature of nervous systems, is not
well understood. Likewise, how clock neurons employ both local and paracrine signals to mediate circadian
timekeeping and entrainment remains enigmatic. Here we propose to study key peptidergic clock neurons in
Drosophila as a model to examine how two neuropeptides released from the same neuron can mediate distinct
behavioral and physiological functions to support robust circadian timekeeping and entrainment. Our work will
not only inform our understanding of circadian timekeeping in the mammalian brain but will also be relevant to
the mechanism of peptide co-release generally.

## Key facts

- **NIH application ID:** 11268334
- **Project number:** 7R01NS118012-05
- **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:** $259,352
- **Award type:** 7
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11268334

## Citation

> US National Institutes of Health, RePORTER application 11268334, Micro-Anatomical Mechanisms of Neuronal Circadian Timekeeping, Output, and Entrainment (7R01NS118012-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11268334. Licensed CC0.

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