Circadian Clock in Mammals
Course duration: 2 h
The suprachiasmatic nucleus (SCN) of the hypothalamus is the primary biological clock regulating circadian rhythms in mammals. Intriguingly, individual SCN neurons express self-sustained circadian oscillations driven by autoregulatory transcription–translation feedback loops. By long-term recording in multielectrode dishes (MEDs), circadian rhythms in firing rate have been demonstrated in dissociated SCN neurons. The mechanism of the circadian clock in individual neurons can be divided into three main components: (a) an intracellular circadian clock that is based on transcription/translation mechanisms, (b) cytoplasmic messenger(s) between the intracellular circadian clock and the effectors located on the internal membrane surface and (c) the circadian-regulated membrane channels that open and close to change the membrane potential and firing rate of SCN neurons from zero frequency during the subjective night to a higher frequency during the subjective day. Series of electrophysiological and histochemical studies were delivered to elucidate the membrane mechanisms responsible for spontaneous activity of SCN neurons and its circadian modulation, or, in other words, to identify the membrane target(s) directly responsible for circadian modulation of firing rate (CMFR). However, this question is still subject of discussion. Based on our experiments with MEDs, we suggest that spike-associated channels are not a primary determinant for CMFR. Studying the mechanisms of spontaneous activity in acutely isolated SCN neurons, potentially containing a functioning circadian clock, we have revealed a novel set of subthreshold, voltage-dependent cation (SVC) channels that are active at resting potential and increase their open probability with membrane depolarization. The single-channel properties of these channels make them a plausible membrane target mediating CMFR. Because during the circadian cycle firing rate of SCN neurons changes from zero to its maximal level, it is natural to suggest that generation of spontaneous activity itself and CMFR represent two aspects of the same membrane mechanism. Therefore, in this Chapter both of these phenomena will be analyzed jointly. A single-compartment, electrophysiological SCN neuron model based on experimental data has been developed. The model is able to mimic the CMFR by modulation of the number of SVC channels or their kinetics. The model also reproduces several experimentally observed detailed features of circadian firing rhythms: the bell-like shape of peaks interrupted by long silent periods, and reduced variability of firing rate near the circadian peak.
Tutors
Dr. Nikolai Kononenko
Country: Ukraine
Place of employment: Bogomoletz Institute of Physiology, NASU, Leading scientific researcher of Department of General Physiology of Nervous System.
Spheres of researches: Biological rhythms of mammals, electrophysiology of neuron, relationship between biochemical reaction in cytoplasm and electrical processes in outer cytoplasmic membrane, plasticity of neuron, oscillations of electrical activity in neuronal networks.
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