A simple model for circadian timing by mammals

Abstract

Circadian timing is structured in such a way as to receive information from the external and internal environments, and its function is the timing organization of the physiological and behavioral processes in a circadian pattern. In mammals, the circadian timing system consists of a group of structures, which includes the suprachiasmatic nucleus (SCN), the intergeniculate leaflet and the pineal gland. Neuron groups working as a biological pacemaker are found in the SCN, forming a biological master clock. We present here a simple model for the circadian timing system of mammals, which is able to reproduce two fundamental characteristics of biological rhythms: the endogenous generation of pulses and synchronization with the light-dark cycle. In this model, the biological pacemaker of the SCN was modeled as a set of 1000 homogeneously distributed coupled oscillators with long-range coupling forming a spherical lattice. The characteristics of the oscillator set were defined taking into account the Kuramoto's oscillator dynamics, but we used a new method for estimating the equilibrium order parameter. Simultaneous activities of the excitatory and inhibitory synapses on the elements of the circadian timing circuit at each instant were modeled by specific equations for synaptic events. All simulation programs were written in Fortran 77, compiled and run on PC DOS computers. Our model exhibited responses in agreement with physiological patterns. The values of output frequency of the oscillator system (maximal value of 3.9 Hz) were of the order of magnitude of the firing frequencies recorded in suprachiasmatic neurons of rodents in vivo and in vitro (from 1.8 to 5.4 Hz).

Systematic Analysis of Circadian Genes in a Population-Based Sample Reveals Association of TIMELESS with Depression and Sleep Disturbance

“…A region of the brain, the suprachiasmatic nucleus (SCN) of the anterior hypothalamus, operates as the master biological clock [2]. Light information goes from the eye to the SCN via the retino-hypothalamic pathway [3], [4], and the neurons within the SCN mediate a series of interlinked autoregulatory transcriptional/translational feedback loops [5], [6]. The key transcriptional activator of the molecular clock consists of a heterodimer between either the clock homolog protein ( CLOCK , alias bHLHe8 ) or the neuronal PAS domain protein 2 ( NPAS2, alias bHLHe9 ) and the aryl hydrocarbon receptor nuclear translocator-like protein ( ARNTL , alias BMAL1 ) that binds to E-box elements in the promoter of three period ( PER ) and two cryptochrome ( CRY ) genes, thereby activating their transcription [7], [8].…”

IV Miguel R. Covian Symposium: new challenges for physiologists

“…Different concepts involving multidisciplinary approaches to the study of epilepsy were also explored. Cardoso et al (19) presented a review of a model for the circadian timing system of mammals to reproduce the endogenous generation and synchronization to the light-dark cycle, which exhibit responses consistent with physiological patterns.…”