# The Generation of Multi-Phasic Circadian Output

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2024 · $16,282

## Abstract

PROJECT SUMMARY/ ABSTRACT
 The purpose of an internal circadian clock is to generate a series of phases - time markers across the
day and night by which di9erent aspects of physiology and behavior (e.g., sleep, hormone release, temperature
elevations) may be aligned to local time for optimal e9iciency. We know a great deal about the molecular mechanisms
of the clock (the timekeeping system) and how it is sensitive to local time. We know much less about circadian output,
and specifically how the clock generates multiple phases across the entire solar day. Such phases are used by other
clock cells, and by non-clock bearing downstream cells and circuits. Our laboratory studies circadian neurophysiology
and the overall goal of this project is to understand the generation and usage of di9erent circadian phasic outputs. The
work is performed in the model system Drosophila. It builds on observations and a model we created from our past
studies of the neural circuit in the Drosophila brain that controls daily locomotor behavior. In the fly brain, ~150
dedicated circadian pacemaker neurons direct daily rhythmic physiology and behavior. These 150 pacemakers are
highly synchronized: they all tell the same time. Our model features the cell-intrinsic molecular clock in all pacemakers
directing a morning phase of heightened neuronal activity. Yet, di9erent subsets of pacemakers are not all active in the
morning, but at di9erent and stereotyped times of the day and night. The diversity of active periods (circadian phases)
is generated primarily by cell interactions (especially neuropeptide modulation) and together these activity periods
represent the multi-phasic outputs of the pacemaker system. Overall, this research program aims to extend and test
this model by providing a cell- and molecular-level understanding for how circadian phase information is transmitted
beyond the pacemaker system and received by downstream target circuits. Our work in Drosophila will likely inform our
understanding of circadian output in the mammalian brain, and will also be relevant more generally to the mechanisms
of neural circuit modulation by neuropeptides.

## Key facts

- **NIH application ID:** 11100868
- **Project number:** 3R35GM149192-02S1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Paul H Taghert
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $16,282
- **Award type:** 3
- **Project period:** 2023-04-05 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11100868

## Citation

> US National Institutes of Health, RePORTER application 11100868, The Generation of Multi-Phasic Circadian Output (3R35GM149192-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11100868. Licensed CC0.

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