# MATERNAL INFLUENCE ON DEVELOPING 24-HOUR PERIODICITY

> **NIH NIH R37** · MASSACHUSETTS GENERAL HOSPITAL · 1994 · $236,244

## Abstract

During fetal life, a biological clock located in the hypothalamic
suprachasmatic nuclei (SCN) is  oscillating.  The mother coordinates
(entrains) the timing of the fetal biological clock to ambient light-dark
conditions.  The experiments proposed in this application use
physiological, and newly developed cellular and molecular approaches to
probe the biology of the fetal SCN.  Our long-term goal is to better
understand the basic mechanisms underlying biological clock function.

First , the signals communicating circadian phase information to the
fetal SCN will be examined.  Periodic feeding or pharmacological doses of
the pineal hormone, melatonin, can entrain the fetuses of SCN-lesioned
pregnant rodents.  Experiments will investigate which aspect of periodic
food presentation entrains the rat fetus.  It will also be determined
whether a physiological pattern of melatonin administration entrains the
fetus.  Potential fetal entraining agents will be examined in vitro by
monitoring the electrical activity rhythm in brains slices containing
fetal SCN.  Second, a dopamine system within the fetal SCN will be
defined.  The expression of c-fos in the fetal SCN can be activated
through a Dl-dopamine receptor suggesting that a functional dopamine
system exists within the fetal SCN.  Experiments will characterize the
components of a dopamine system in the fetal hypothalamus, assess the
functional significance of this dopamine system, and investigate the
potential role of other transmitter systems in the fetal SCN.  Third, the
functional properties of migrating SCN neurons will be elucidated.
Dopamine Dl- receptor mRNA will be used to identify SCN neurons during
migration.  This will permit investigation of the circadian properties of
migrating SCN neurons.  Fourth, the oscillatory properties of the
developing SCN will be investigated, utilizing multimicroelectrode plates
to record electrical activity from cultured neurons.  The ability of
fetal SCN cells to form a functional circadian clock following
dissociation will be used to examine the functional interactions among
SCN cells which develop to form, a circadian clock in vitro.  This system
will also be used to determine whether single SCN cells express circadian
oscillations in firing rate in vitro.

Circadian variations affect virtually all aspects of human physiology and
can contribute to pathophysiological states.  Thus, increased
understanding of the basic mechanisms of biological clock function may
facilitate the development of better treatment strategies for a wide
range of disorders.

## Key facts

- **NIH application ID:** 2197093
- **Project number:** 5R37HD014427-13
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **SAM.gov UEI:** FLJ7DQKLL226
- **Principal Investigator:** STEVEN M. REPPERT
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $236,244
- **Award type:** 5
- **Project period:** 1981-04-01 → 1997-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197093

## Citation

> US National Institutes of Health, RePORTER application 2197093, MATERNAL INFLUENCE ON DEVELOPING 24-HOUR PERIODICITY (5R37HD014427-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197093. Licensed CC0.

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