Dataset Information

A Mathematical Model to Characterize the Role of Light Adaptation in Mammalian Circadian Clock.

ABSTRACT: In response to a light stimulus, the mammalian circadian clock first dramatically increases the expression of Per1 mRNA, and then drops to a baseline even when light persists. This phenomenon is known as light adaptation, which has been experimentally proven to be related to the CRTC1-SIK1 pathway in suprachiasmatic nucleus (SCN). However, the role of this light adaptation in the circadian rhythm remains to be elucidated. To reveal the in-depth function of light adaptation and the underlying dynamics, we proposed a mathematical model for the CRTC1-SIK1 network and coupled it to a mammalian circadian model. The simulation result proved that the light adaptation is achieved by the self-inhibition of the CRTC1/CREB complex. Also, consistently with experimental observations, this adaptation mechanism can limit the phase response to short-term light stimulus, and it also restricts the rate of the phase shift in a jet lag protocol to avoid overly rapid re-entrainment. More importantly, this light adaptation is predicted to prevent the singularity behavior in the cell population, which represents the abolishment of circadian rhythmicity due to desynchronization of oscillating cells. Furthermore, it has been shown to provide refractoriness to successive stimuli with short gap. Therefore, we concluded that the light adaptation generated by the CRTC1-SIK1 pathway in the SCN provides a robust mechanism, allowing the circadian system to maintain homeostasis in the presence of light perturbations. These results not only give new insights into the dynamics of light adaptation from a computational perspective but also lead us to formulate hypotheses about the related physiological significance.

SUBMITTER: Shi Y

PROVIDER: S-EPMC8691188 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Seasonal light cycles influence multiple physiological functions and are mediated through photoperiodic encoding by the circadian system. Despite our knowledge of the strong connection between seasonal light input and downstream circadian changes, less is known about the specific components of seasonal light cycles that are encoded and induce persistent changes in the circadian system. Using combinations of 3 T cycles (23, 24, 26 h) and 2 photoperiods per T cycle (long and short, with duty cycles scaled to each T cycle), we investigate the after-effects of entrainment to these 6 light cycles. We measure locomotor behavior duration (α), period (τ), and entrained phase angle (ψ) in vivo and SCN phase distribution (σφ), τ, and ψ ex vivo to refine our understanding of critical light components for influencing particular circadian properties. We find that both photoperiod and T-cycle length drive determination of in vivo ψ but differentially influence after-effects in α and τ, with photoperiod driving changes in α and photoperiod length and T-cycle length combining to influence τ. Using skeleton photoperiods, we demonstrate that in vivo ψ is determined by both parametric and nonparametric components, while changes in α are driven nonparametrically. Within the ex vivo SCN, we find that ψ and σφ of the PER2∷LUCIFERASE rhythm follow closely with their likely behavioral counterparts (ψ and α of the locomotor activity rhythm) while also confirming previous reports of τ after-effects of gene expression rhythms showing negative correlations with behavioral τ after-effects in response to T cycles. We demonstrate that within-SCN σφ changes, thought to underlie α changes in vivo, are induced primarily nonparametrically. Taken together, our results demonstrate that distinct components of seasonal light input differentially influence ψ, α, and τ and suggest the possibility of separate mechanisms driving the persistent changes in circadian behaviors mediated by seasonal light.

Dataset Information

A Mathematical Model to Characterize the Role of Light Adaptation in Mammalian Circadian Clock.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets