1. Yeh P-T, Jhan K-C, Chua E-P, Chen W-C, Chu S-W, Wu S-C, Chen S-K*. Discrete photoentrainment of mammalian central clock is regulated by bi-stable dynamic network in the suprachiasmatic nucleus. Nat Commun 16, 3331 (2025). https://doi.org/10.1038/s41467-025-58661-1
2. Huang Y-Fequal, Liao P-Yequal, Yu J-H, Chen S-K (Alen)*. Light disrupts social memory via a retina-to-supraoptic nucleus circuit. EMBO Rep. 2023 Aug 2:e56839. doi: 10.15252/embr.202356839.
3. Liang F, Chen C-Y, Li Y-P, Ke Y-C, Ho E-P, Jeng C-F, Lin C-H*, Chen S-K*. Early Dysbiosis and Dampened Gut Microbe Oscillation Precede Motor Dysfunction and Neuropathology in Animal Models of Parkinson's Disease. J Parkinsons Dis. 2022;12(8):2423-2440. doi: 10.3233/JPD-223431.
4. Lee C-C, Liang F, Lee I-C, Lu T-H, Shan Y-Y, Jeng C-F, Zou Y-F, Yu H-T, Chen S-K (Alen) *. External light-dark cycle shapes gut microbiota through intrinsically photosensitive retinal ganglion cells. EMBO Rep. 2022 Jun 7;23(6):e52316.
5. Lin M-S, Liao P-Y, Chen H-M, Chang C-P, Chen S-K*, Chern Y-J*. Degeneration of ipRGCs in mouse models of Huntington's Disease disrupts non-image forming behaviors prior to motor impairment. J. Neurosci. 20 Feb 2019, 39(8) 1505-1524
6. Fan M-Y, Chang Y-T, Chen C-L, Wang W-H, Pan M-K, Chen W-P, Huang W-Y, Xug Z, Huang H-E, Cheng T, Plikush MV, Chen S-K*, Lin S-J*. External light activates hair follicle stem cells through eyes via an ipRGC–SCN–sympathetic neural pathway. PNAS. 2018 Jul 17;115(29)
7. Prigge CL, Yeh P-T, Liou N-F, Lee C-C, You S-F, Liu L-L, McNeill DS, Chew KS, Hattar S, Chen S-K*, and Zhang D-Q*. M1 ipRGCs Influence Visual Function through Retrograde Signaling in the Retina. J. Neurosci. 2016; 36(27):7184 -7197.
8. Fernandez DCequal, Chang Y-Tequal, Hattar S, Chen S-K*. Architecture of retinal projections to the central circadian pacemaker. PNAS. 2016; 113(21):6047-52.
|
The biological clock, housed in the suprachiasmatic nucleus (SCN) of the hypothalamus, synchronizes with the environmental light-dark cycle through circadian photoentrainment. This process in mammals demonstrates discrete light responses, causing a phase delay during the early subjective night and a phase advance during the late subjective night. However, the specific neuronal circuitry within the SCN that generates these distinct, time-gated behavioral outputs remains poorly understood. We investigated the SCN's functional network by modulating and observing neuronal activity at the single-cell level during critical circadian times (CT).
We employed in vivo two-photon calcium imaging in the SCN. Our population-wide recording revealed that most SCN neurons exhibit diverse and highly stochastic light responses, often showing different response types across repeated trials. Critically, cross-time correlation analysis indicated that light responses for individual neurons varied significantly across different ZT (Zeitgeber Time) points, suggesting a dynamic functional network rather than a stable, time-independent circuit. Through comprehensive analysis of responses across ZT 8, ZT 16, and ZT 22, we identified three distinct neuronal groups : a small group (Group 1, ~11.5%) showing persistent positive activation at ZT 16; another small group (Group 2, ~4.4%) exhibiting consistent inhibition only at ZT 22; and a large majority (Group 3, ~84.1%) displaying highly dynamic, inconsistent responses. We propose that Group 1 and Group 2 function as "outcome" neurons driving phase shift at delay or advance times, respectively, while Group 3 acts as the "computational" unit employing dynamic population coding. These findings suggest a dynamic bi-stable network model where phase shifts arise from a functional circuit integrating signals to select outcome neurons, moving beyond the traditional hierarchical or labeled-line principles of SCN organization. This discovery lays the groundwork for future research into the time-gated mechanisms of circadian photoentrainment.
|