Parametric Models of the Circadian Pacemaker in Controlled Lighting Conditions
Creators: name: Usmani, Imran Masood
Publisher: name: University of Surrey
Year: 2022
Subjects: circadian pacemaker
zeitgebers
controlled lighting conditions
parametric models
phase-only models
two-dimensional models
Circadian Rhythms

description: In mammals, the circadian pacemaker is a biological clock responsible for the timing of many
description: of the body's circadian rhythms, including the sleep-wake cycle. Mathematical models of the
description: circadian pacemaker could fi nd applications in the treatment of sleep disorders or in medical
description: chronotherapy. Parametric models are phenomenological models that are widely used to model
description: the circadian systems of diurnal animals. However, current models of the circadian pacemaker
description: in humans are based on limited data, and they often produce inaccurate predictions when they
description: are used in novel settings. We consider one- and two-dimensional parametric models, and we
description: explore how the design of models is informed by experimental data. Our aim is to design models
description: that accurately reproduce data from various experimental studies.<br>
description: <br>
description: The circadian pacemaker generates rhythms even in the absence of time cues, or zeitgebers.
description: However, the pacemaker is responsive to light, which is how it synchronizes, or entrains, to the
description: day-night cycle on the Earth's surface. In parametric models, the self-sustaining activity of
description: the pacemaker is modelled by a clock with some intrinsic velocity and the effect of light is to
description: modulate the velocity of the clock. The velocity response of the clock to light is the product of
description: a tonic stimulus and a response function, which describes the sensitivity of the clock to light as
description: a function of the state of the clock.<br>
description: <br>
description: In one-dimensional, or phase-only, parametric models, we show that it is necessary to make
description: simplifying assumptions about the response function to design models based on data from studies
description: in controlled lighting conditions. This motivates us to consider 'simple' clock models in which
description: the response function is sinusoidal. We obtain two specific results in our study of phase-only
description: models. Firstly, we show that the shorter period of sighted humans in forced desynchrony
description: compared to the period of blind people can be explained by a model whose response function
description: has a larger advance region than delay region. Secondly, we show that simple clock models with
description: different response functions are required to reproduce the effects of light of different intensity
description: in studies of humans in controlled lighting conditions. This challenges the prevailing view in
description: circadian biology that the sensitivity of the pacemaker to light does not vary in different lighting
description: conditions.<br>
description: <br>
description: We investigate how two-dimensional parametric models can reproduce the phenomena of type
description: 0 phase resetting and after-effects. We show that the strength of attraction of the unperturbed
description: limit cycle of the clock is a key feature of the models. We use a clock with a strongly attracting
description: limit cycle to reproduce Khalsa's type 0 phase transition curve in humans. We use a clock with
description: a weakly attracting limit cycle to reproduce after-effects in the four-striped grass mouse.<br>