To identify key hub cells driving SCN network synchrony, we simulated the experimentally inferred SCN maps in 6 mice and tested the impact of ablating various cell types on networks' ability to synchronize. (9/n)
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VIP hubs drive SCN circadian synchrony: We found a topologically unique group of VIP hub neurons that generate and broadcast signals with their extensive and long-range connections. SCN networks did not synchronize on ablating the VIP hubs but not AVP cells. (10/n)
All signals converged on the dorsal 'sink' cells (including the AVP cells) which were not essential for driving SCN synchrony. We also identified 'bridge' cells in the central SCN that couple information flow across the modules & likely underlie seasonal SCN reorganization (11/n)
Network wiring shapes SCN emergent properties: Simulated SCN cell behavior showed a strong correlation with their corresponding experimentally recorded explants. In silico ventral SCN synchronized faster and also recapitulated the characteristic wave of PER2 expression. (12/n)
In conclusion, we reveal that robust circadian timekeeping in mammalian SCN arises from functionally heterogeneous cell types, organized into two cellular networks and driven by a subset of VIP hubs neurons with unique connectivity topology. end!
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