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January 17, 2026Advanced Science0 citationsOpen Access

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

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HKHan KuiMLMeimei LiaoJZJingpeng Zhang

Key Points

  • To explore how vasoactive intestinal polypeptide (VIP) regulates synchronization in the suprachiasmatic nucleus (SCN).
  • Developed an automated culture system for SCN slices and dissociated cells (BaSIC)
  • Monitored tissue responses to various stimuli in real-time
  • Examined VIP's effects on circadian rhythm timing and amplitude shifts
  • VIP pulsing resets circadian rhythm by synchronizing phase and amplitude
  • Rapid reduction of Period 2 (PER2) protein levels was observed
  • Mathematical modeling confirmed VIP's role in reducing PER2

Abstract

ABSTRACT 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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Cite This Study

Kui et al. (2026) studied this question.

synapsesocial.com/papers/696b26b2d2a12237a934a011https://doi.org/10.1002/advs.202511069
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