An Automated Organotypic SCN Culture System Revealing Novel Insights into VIP Regulation of Circadian Rhythm

🥈 Top 2% JournalJan 15, 2026Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Automated 3D Brain Clock Tissue Study Reveals New Details on VIP’s Role in Daily Rhythms

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

VIP pulsing rapidly resets the circadian rhythm by synchronizing both phase and amplitude through a swift reduction of Period 2 (PER2) protein.

The suprachiasmatic nucleus (SCN) is crucial for regulating circadian rhythms in mammals.
Individual SCN neurons can oscillate independently but are synchronized through intercellular signaling involving vasoactive intestinal polypeptide (VIP).
The molecular mechanism by which VIP synchronizes SCN neurons remains unclear.
An automated culture system named 'brain-slice-in-a-chamber' (BaSIC) allows for enhanced study of SCN tissue responses.
VIP is associated with a rapid reduction in PER2 protein, which may facilitate the synchronization of circadian rhythms.

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In mammals, the suprachiasmatic nucleus (SCN) functions as the primary driver of circadian rhythm. Although individual SCN neurons exhibit cell-autonomous oscillations, intercellular communication-mediated by neural peptides such as vasoactive intestinal polypeptide (VIP)-synchronizes their rhythms. However, the precise molecular mechanism by which VIP facilitates SCN synchronization remains elusive. Here, we introduce an automated ex vivo culture system, termed 'brain-slice-in-a-chamber' (BaSIC), tailored for SCN slices, as well as dissociated cells culture. This apparatus automates medium exchange and ensures optimal control over temperature and humidity, ensuring a stable internal environment conducive to tissue culture. Furthermore, BaSIC enables real-time observation of tissue responses to diverse but programmed stimuli. Using BaSIC, we demonstrate that VIP pulsing rapidly resets the circadian rhythm by synchronizing both phase and amplitude through a swift reduction of Period 2 (PER2) protein. Mathematical modeling, coupled with experimental validation, further suggests that VIP promotes the rapid reduction of PER2. Our findings, facilitated by BaSIC, provide new insights into SCN neuron synchronization, paving the way for advanced studies in chronobiology, with potential therapeutic applications for circadian disorders.

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