Dataset Information

Astrocytes Regulate Daily Rhythms in the Suprachiasmatic Nucleus and Behavior.

ABSTRACT: Astrocytes are active partners in neural information processing [1, 2]. However, the roles of astrocytes in regulating behavior remain unclear [3, 4]. Because astrocytes have persistent circadian clock gene expression and ATP release in vitro [5-8], we hypothesized that they regulate daily rhythms in neurons and behavior. Here, we demonstrated that daily rhythms in astrocytes within the mammalian master circadian pacemaker, the suprachiasmatic nucleus (SCN), determine the period of wheel-running activity. Ablating the essential clock gene Bmal1 specifically in SCN astrocytes lengthened the circadian period of clock gene expression in the SCN and in locomotor behavior. Similarly, excision of the short-period CK1? tau mutation specifically from SCN astrocytes resulted in lengthened rhythms in the SCN and behavior. These results indicate that astrocytes within the SCN communicate to neurons to determine circadian rhythms in physiology and in rest activity.

SUBMITTER: Tso CF

PROVIDER: S-EPMC5380592 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Astrocytes Regulate Daily Rhythms in the Suprachiasmatic Nucleus and Behavior.

Tso Chak Foon CF Simon Tatiana T Greenlaw Alison C AC Puri Tanvi T Mieda Michihiro M Herzog Erik D ED

Current biology : CB 20170323 7

Astrocytes are active partners in neural information processing [1, 2]. However, the roles of astrocytes in regulating behavior remain unclear [3, 4]. Because astrocytes have persistent circadian clock gene expression and ATP release in vitro [5-8], we hypothesized that they regulate daily rhythms in neurons and behavior. Here, we demonstrated that daily rhythms in astrocytes within the mammalian master circadian pacemaker, the suprachiasmatic nucleus (SCN), determine the period of wheel-running ...[more]

PMID: 28343966

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Project description:In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus coordinates daily rhythms including sleep-wake, hormone release, and gene expression. The cells of the SCN must synchronize to each other to drive these circadian rhythms in the rest of the body. The ontogeny of circadian cycling and intercellular coupling in the SCN remains poorly understood. Recent in vitro studies have recorded circadian rhythms from the whole embryonic SCN. Here, we tracked the onset and precision of rhythms in PERIOD2 (PER2), a clock protein, within the SCN isolated from embryonic and postnatal mice of undetermined sex. We found that a few SCN cells developed circadian periodicity in PER2 by 14.5 d after mating (E14.5) with no evidence for daily cycling on E13.5. On E15.5, the fraction of competent oscillators increased dramatically corresponding with stabilization of their circadian periods. The cells of the SCN harvested at E15.5 expressed sustained, synchronous daily rhythms. By postnatal day 2 (P2), SCN oscillators displayed the daily, dorsal-ventral phase wave in clock gene expression typical of the adult SCN. Strikingly, vasoactive intestinal polypeptide (VIP), a neuropeptide critical for synchrony in the adult SCN, and its receptor, VPAC2R, reached detectable levels after birth and after the onset of circadian synchrony. Antagonists of GABA or VIP signaling or action potentials did not disrupt circadian synchrony in the E15.5 SCN. We conclude that endogenous daily rhythms in the fetal SCN begin with few noisy oscillators on E14.5, followed by widespread oscillations that rapidly synchronize on E15.5 by an unknown mechanism.SIGNIFICANCE STATEMENT We recorded the onset of PER2 circadian oscillations during embryonic development in the mouse SCN. When isolated at E13.5, the anlagen of the SCN expresses high, arrhythmic PER2. In contrast, a few cells show noisy circadian rhythms in the isolated E14.5 SCN and most show reliable, self-sustained, synchronized rhythms in the E15.5 SCN. Strikingly, this synchrony at E15.5 appears before expression of VIP or its receptor and persists in the presence of blockers of VIP, GABA or neuronal firing. Finally, the dorsal-ventral phase wave of PER2 typical of the adult SCN appears ?P2, indicating that multiple signals may mediate circadian synchrony during the ontogeny of the SCN.

Dataset Information

Astrocytes Regulate Daily Rhythms in the Suprachiasmatic Nucleus and Behavior.

Publications

Astrocytes Regulate Daily Rhythms in the Suprachiasmatic Nucleus and Behavior.

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