Mechanism of bilateral communication in the suprachiasmatic nucleus

Michel, Stephan; Marek, Roger; vanderLeest, Henk Tjebbe; Vansteensel, Mariska J.; Schwartz, William J.; Colwell, Christopher S.; Meijer, Johanna H.

doi:10.1111/ejn.12109

Cited by 34 publications

(35 citation statements)

References 62 publications

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“…This possible involvement of the glutamate receptor is especially interesting, because the glutamate receptor has also been implicated in communication between the SCN and the RHT, which occurs in the core SCN region (53). Thus, our results support the hypothesis that antiphasic oscillation between SCN halves in constant light is made possible by distinct signaling mechanisms in the SCN rather than a weaker coupling strength between halves (52,54).…”

Section: B Asupporting

confidence: 83%

“…The SCN is often thought to be most tightly connected within each half, given the ability of the left and right SCN to oscillate in antiphase in animals exposed to constant light (50,51). However, tight bilateral coupling is reflective of previous studies that showed significant coupling between the halves and further implicates the glutamate receptor in this communication (52). This possible involvement of the glutamate receptor is especially interesting, because the glutamate receptor has also been implicated in communication between the SCN and the RHT, which occurs in the core SCN region (53).…”

Section: B Amentioning

confidence: 99%

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Functional network inference of the suprachiasmatic nucleus

Abel

Meeker

Granados‐Fuentes

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

100

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In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators communicate within a neuronal network to generate precise system-wide circadian rhythms. Although the intracellular genetic oscillator and intercellular biochemical coupling mechanisms have been examined previously, the network topology driving synchronization of the SCN has not been elucidated. This network has been particularly challenging to probe, due to its oscillatory components and slow coupling timescale. In this work, we investigated the SCN network at a single-cell resolution through a chemically induced desynchronization. We then inferred functional connections in the SCN by applying the maximal information coefficient statistic to bioluminescence reporter data from individual neurons while they resynchronized their circadian cycling. Our results demonstrate that the functional network of circadian cells associated with resynchronization has small-world characteristics, with a node degree distribution that is exponential. We show that hubs of this small-world network are preferentially located in the central SCN, with sparsely connected shells surrounding these cores. Finally, we used two computational models of circadian neurons to validate our predictions of network structure.

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Section: B Asupporting

confidence: 83%

Section: B Amentioning

confidence: 99%

Functional network inference of the suprachiasmatic nucleus

Abel

Meeker

Granados‐Fuentes

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

100

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“…Unilateral lesion of the SCN abolished the splitting and established a single rhythm of behavioral activity (Pickard and Turek 1982). In normal conditions, the left and right SCN are strongly connected with each other even in isolated culture (Michel et al 2013), and the functional connection is important for coupling of their free-running rhythms, as observed in wild-type SCN slices over 10 d (Fig. 2).…”

Section: Discussionmentioning

confidence: 75%

CaMKII is essential for the cellular clock and coupling between morning and evening behavioral rhythms

et al. 2014

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Daily behavioral rhythms in mammals are governed by the central circadian clock, located in the suprachiasmatic nucleus (SCN). The behavioral rhythms persist even in constant darkness, with a stable activity time due to coupling between two oscillators that determine the morning and evening activities. Accumulating evidence supports a prerequisite role for Ca 2+ in the robust oscillation of the SCN, yet the underlying molecular mechanism remains elusive. Here, we show that Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) activity is essential for not only the cellular oscillation but also synchronization among oscillators in the SCN. A kinase-dead mutation in mouse CaMKIIa weakened the behavioral rhythmicity and elicited decoupling between the morning and evening activity rhythms, sometimes causing arrhythmicity. In the mutant SCN, the right and left nuclei showed uncoupled oscillations. Cellular and biochemical analyses revealed that Ca 2+ -calmodulin-CaMKII signaling contributes to activation of E-box-dependent gene expression through promoting dimerization of circadian locomotor output cycles kaput (CLOCK) and brain and muscle Arnt-like protein 1 (BMAL1). These results demonstrate a dual role of CaMKII as a component of cell-autonomous clockwork and as a synchronizer integrating circadian behavioral activities.

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“…Ca 2+ measurements were performed as described previously (35). Brain slices that included the SCN were loaded with the ratiometric Ca 2+ indicator dye fura-2-acetoxymethyl ester (Fura-2-AM).…”

Section: Methodsmentioning

confidence: 99%

Seasonal induction of GABAergic excitation in the central mammalian clock

Farajnia

Westering

Meijer

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

104

129

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The balance between excitation and inhibition is essential for the proper function of neuronal networks in the brain. The inhibitory neurotransmitter γ-aminobutyric acid (GABA) contributes to the network dynamics within the suprachiasmatic nucleus (SCN), which is involved in seasonal encoding. We investigated GABAergic activity and observed mainly inhibitory action in SCN neurons of mice exposed to a short-day photoperiod. Remarkably, the GABAergic activity in a long-day photoperiod shifts from inhibition toward excitation. The mechanistic basis for this appears to be a change in the equilibrium potential of GABA-evoked current. These results emphasize that environmental conditions can have substantial effects on the function of a key neurotransmitter in the central nervous system.S easonal changes in the photoperiod of the Earth's temperate zones affect the behavior and physiology of many organisms (1). The central circadian clock, located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus, can adapt to changes in day length and displays a compressed circadian pattern of electrical activity in short winter days and a decompressed pattern in long summer days (2). This pattern is based on a change in the phase distribution of the activity patterns of individual neurons, which becomes broad in the summer and narrow in the winter (3). The mechanisms that mediate and regulate photoperiod-induced phase distributions are currently not known.The neurotransmitter γ-aminobutyric acid (GABA) is believed to be involved in the phase adjustment and synchronization of the SCN neuronal network (4, 5). GABA and its receptors are expressed in most SCN neurons (6). GABAergic inhibition has been indicated to be important in normal physiological function within the brain. Alterations in this system (i.e., less inhibition) are shown to cause neurological disorders, such as epilepsy and autism (7,8). In addition to its classical inhibitory function within the SCN network, GABA has more recently been shown to also act as an excitatory transmitter, although its exact role is uncertain (4, 9-13). To understand the influence of photoperiod on GABAergic function, we studied synaptic activity, using patch clamp, and GABAergic responses, using Ca 2+ imaging techniques, in the SCN of mice adjusted to long-day and short-day photoperiods. We hypothesized that the narrow, synchronized phase distribution of active neurons during short-day photoperiods would result in increased synaptic activity during the day. Surprisingly, however, exposure to a short-day photoperiod decreased the frequency of spontaneous GABAergic synaptic events compared with the long-day photoperiod.Subsequently, we tested the effect of photoperiod on GABAinduced excitation in the SCN neuronal network. Ca 2+ transients were measured in response to GABA stimulation in long-day and short-day photoperiods. Interestingly, of all cells from the long-day photoperiod, 40% were excitatory and 36% were inhibitory. In contrast, in the short-day photoperiod, 28% of the c...

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Mechanism of bilateral communication in the suprachiasmatic nucleus

Cited by 34 publications

References 62 publications

Functional network inference of the suprachiasmatic nucleus

Functional network inference of the suprachiasmatic nucleus

CaMKII is essential for the cellular clock and coupling between morning and evening behavioral rhythms

Seasonal induction of GABAergic excitation in the central mammalian clock

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