Antiphase Oscillation of the Left and Right Suprachiasmatic Nuclei

la, Horacio O. de; Iglesia,; Meyer, Jennifer L.; Carpino, Alan; Schwartz, William J.

doi:10.1126/science.290.5492.799

Cited by 253 publications

(65 citation statements)

References 34 publications

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“…It seems likely that input from the SCN stimulates glia to pull away and expose GnRH neurons prior to the large increase in GnRH peptide release associated with the subsequent LH surge. Hamsters that undergo SCN ‘splitting’ have two smaller LH surges 12 h out of phase with one another [39,40]. In those studies, confocal images showing cFOS activation in GnRH neurons with direct connections from the SCN found only half of the GnRH population was activated at either time point.…”

Section: Discussionmentioning

confidence: 99%

In vivo Circadian Rhythms in Gonadotropin-Releasing Hormone Neurons

Hickok

Tischkau

2009

Neuroendocrinology

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Although it is generally accepted that the circadian clock provides a timing signal for the luteinizing hormone (LH) surge, mechanistic explanations of this phenomenon remain underexplored. It is known, for example, that circadian locomotor output cycles kaput (clock) mutant mice have severely dampened LH surges, but whether this phenotype derives from a loss of circadian rhythmicity in the suprachiasmatic nucleus (SCN) or altered circadian function in gonadotropin-releasing hormone (GnRH) neurons has not been resolved. GnRH neurons can be stimulated to cycle with a circadian period in vitro and disruption of that cycle disturbs secretion of the GnRH decapeptide. We show that both period-2 (PER2) and brain muscle Arnt-like-1 (BMAL1) proteins cycle with a circadian period in the GnRH population in vivo. PER2 and BMAL1 expression both oscillate with a 24-hour period, with PER2 peaking during the night and BMAL1 peaking during the day. The population, however, is not as homogeneous as other oscillatory tissues with only about 50% of the population sharing peak expression levels of BMAL1 at zeitgeber time 4 (ZT4) and PER2 at ZT16. Further, a light pulse that induced a phase delay in the activity rhythm of the GnRH-eGFP mice caused a similar delay in peak expression levels of BMAL1 and PER2. These studies provide direct evidence for a functional circadian clock in native GnRH neurons with a phase that closely follows that of the SCN.

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Section: Discussionmentioning

confidence: 99%

In vivo Circadian Rhythms in Gonadotropin-Releasing Hormone Neurons

Hickok

Tischkau

2009

Neuroendocrinology

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“…DD rapidly restores the split rhythm to its normal unsplit state (figure 1b). Recent data show that the SCN is dramatically reorganized in the split condition; its left and right halves continue to oscillate with a circadian period but now in anti-phase rather than in-phase (de la Iglesia et al 2000). It has been proposed that this reconfigured phasing of cellular oscillators within the SCN tissue leads to the frequency doubling of the locomotor rhythm.…”

Section: Introductionmentioning

confidence: 99%

Design principles for phase-splitting behaviour of coupled cellular oscillators: clues from hamsters with ‘split’ circadian rhythms

Indic

Schwartz

Paydarfar

2007

J. R. Soc. Interface.

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Nonlinear interactions among coupled cellular oscillators are likely to underlie a variety of complex rhythmic behaviours. Here we consider the case of one such behaviour, a doubling of rhythm frequency caused by the spontaneous splitting of a population of synchronized oscillators into two subgroups each oscillating in anti-phase ( phase-splitting). An example of biological phase-splitting is the frequency doubling of the circadian locomotor rhythm in hamsters housed in constant light, in which the pacemaker in the suprachiasmatic nucleus (SCN) is reconfigured with its left and right halves oscillating in anti-phase. We apply the theory of coupled phase oscillators to show that stable phase-splitting requires the presence of negative coupling terms, through delayed and/or inhibitory interactions. We also find that the inclusion of real biological constraints (that the SCN contains a finite number of nonidentical noisy oscillators) implies the existence of an underlying non-uniform network architecture, in which the population of oscillators must interact through at least two types of connections. We propose that a key design principle for the frequency doubling of a population of biological oscillators is inhomogeneity of oscillator coupling.

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“…Coupling among rhythmic elements can lead to synchronization, where a number of rhythmic elements organize into a single group with a uniform phase and frequency. Such synchronization can lead to coherent light emission from laser systems (Petrov et al 1997;Oliva & Strogatz 2001), neuronal clustering in the suprachiasmatic nucleus (Iglesia et al 2000;Yamaguchi et al 2003), oscillations in chemical systems (Epstein & Pojman 1998), epileptic events (Traub & Wong 1982) and Parkinsonian tremors (Tass 1999).…”

Section: Introductionmentioning

confidence: 99%

“…This twooscillator system represents a canonical model for a large class of rhythmic biological systems (Winfree 1980;Iglesia et al 2000) and incorporates many of the non-idealities that are present in typical experimental systems, yet has a simple analytical solution. Heterogeneities are common in experimental and natural rhythmic systems where the intrinsic oscillator frequency is not under experimental control.…”

Section: Introductionmentioning

confidence: 99%

Synchronization engineering: tuning the phase relationship between dissimilar oscillators using nonlinear feedback

Rusin

Kori

Kiss

et al. 2010

Phil. Trans. R. Soc. A.

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A mild, nonlinear, time-delayed feedback signal was applied to two heterogeneous oscillators in order to synchronize their frequencies with an arbitrary and controllable phase difference. The feedback was designed using phase models constructed from experimental measurements of the intrinsic dynamical properties of the oscillators. The feedback signal produced an interaction function that corresponds to the desired collective behaviour. The synchronized phase difference between the elements can be tuned to any value on the interval 0 and 2p by shifting the phase of the interaction function using the feedback delay. Numerical simulations were conducted and experiments carried out with electrochemical oscillators.

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Antiphase Oscillation of the Left and Right Suprachiasmatic Nuclei

Cited by 253 publications

References 34 publications

In vivo Circadian Rhythms in Gonadotropin-Releasing Hormone Neurons

In vivo Circadian Rhythms in Gonadotropin-Releasing Hormone Neurons

Design principles for phase-splitting behaviour of coupled cellular oscillators: clues from hamsters with ‘split’ circadian rhythms

Synchronization engineering: tuning the phase relationship between dissimilar oscillators using nonlinear feedback

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