Synchronization of Cellular Clocks in the Suprachiasmatic Nucleus

Abstract

Individual cellular clocks in the suprachiasmatic nucleus (SCN), the circadian center, are integrated into a stable and robust pacemaker with a period length of about 24 hours. We used real-time analysis of gene expression to show synchronized rhythms of clock gene transcription across hundreds of neurons within the mammalian SCN in organotypic slice culture. Differentially phased neuronal clocks are topographically arranged across the SCN. A protein synthesis inhibitor set all cell clocks to the same initial phase and, after withdrawal, intrinsic interactions among cell clocks reestablished the stable program of gene expression across the assemblage. Na+-dependent action potentials contributed to establishing cellular synchrony and maintaining spontaneous oscillation across the SCN.

Development of the mouse suprachiasmatic nucleus: Determination of time of cell origin and spatial arrangements within the nucleus

“…They differ with respect to the expression of specific neurotransmitters and neuropeptides [21,31], their efferent and afferent connections [1,22], and their neurophysiological firing patterns [14]. In addition, isolated SCN cells express different circadian periods [13,32] and, within the nucleus, different individual cells or groups of cells oscillate with different phases [25,33].…”

Phase organization of circadian oscillators in extended gate and oscillator models

“…3 blue). Experimental results suggest that although the overall phase distribution is wide 19,24 , the phase difference between individual neurons is conserved 19 . Therefore, it is hard to explain those experimental results within such a simple gate-oscillator model.…”

“…Since the mPer1 and mPer2 gene expression in shell SCN follows specific spatial-temporal pattern 19,28 , and the phase reset effect induced by light is carried out by activating mPer1 and mPer2, the author tries to model this topographical complexity of SCN by the propagation delay of the resetting signal. It is convenient to include signal delay in the gate-oscillator scheme while it is not very easy to do so in a model that relies on local or global coupling only.…”

“…It is impressive that such a simple model could account for the complex behavior of SCN in many aspects 22 . Moreover, a strong support for this model is the presence of anti-phase neurons within the shell SCN 6,19,23,24 , which is difficult to explain by coupling only 25 . By replacing the original linear phase resetting function with a sigmoid one, Yan et al have modeled the anti-phase populations of neurons in the gate and oscillator model 6 .…”

“…Destruction of these cells leads to arrhythmic behavior. Moreover, the shell SCN becomes arrhythmic because of lacking synchrony 18,19 . These findings have motivated Antle et al to propose the gate and oscillator model 20,21 , in which the gate cells (core SCN neurons) send resetting signals, which make the shell neurons' phase more compact, to the oscillator cells (shell SCN).…”