Exploring Spatiotemporal Organization of SCN Circuits

Yan, Lili; Karatsoreos, Ilia N.; LeSauter, Joseph; Welsh, David K.; Kay, Steve A.; Foley, Duncan K.; Silver, Rae

doi:10.1101/sqb.2007.72.037

Cited by 104 publications

(119 citation statements)

References 123 publications

(133 reference statements)

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“…This metastable network state in the SCN is programmable by the seasonal day length and persists on a timescale much longer than the circadian timescale (44). The clock neurons in the SCN also exhibit spatiotemporal patterns in the oscillatory clock gene expressions (13,45). Metastability in the brain clock was noticed even in the early days of circadian biology and has long been thought to be relevant for encoding seasonal rhythms (26).…”

Section: Discussionmentioning

confidence: 99%

GABA-mediated repulsive coupling between circadian clock neurons in the SCN encodes seasonal time

Myung

Hong

DeWoskin

et al. 2015

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

146

229

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The mammalian suprachiasmatic nucleus (SCN) forms not only the master circadian clock but also a seasonal clock. This neural network of ∼10,000 circadian oscillators encodes season-dependent day-length changes through a largely unknown mechanism. We show that region-intrinsic changes in the SCN fine-tune the degree of network synchrony and reorganize the phase relationship among circadian oscillators to represent day length. We measure oscillations of the clock gene Bmal1, at single-cell and regional levels in cultured SCN explanted from animals raised under short or long days. Coupling estimation using the Kuramoto framework reveals that the network has couplings that can be both phase-attractive (synchronizing) and -repulsive (desynchronizing). The phase gap between the dorsal and ventral regions increases and the overall period of the SCN shortens with longer day length. We find that one of the underlying physiological mechanisms is the modulation of the intracellular chloride concentration, which can adjust the strength and polarity of the ionotropic GABA A -mediated synaptic input. We show that increasing daylength changes the pattern of chloride transporter expression, yielding more excitatory GABA synaptic input, and that blocking GABA A signaling or the chloride transporter disrupts the unique phase and period organization induced by the day length. We test the consequences of this tunable GABA coupling in the context of excitation-inhibition balance through detailed realistic modeling. These results indicate that the network encoding of seasonal time is controlled by modulation of intracellular chloride, which determines the phase relationship among and period difference between the dorsal and ventral SCN.day-length encoding | repulsive coupling | SCN | GABA | chloride T he physiological and behavioral rhythms of all life on earth are bound to the Earth's rotational cycle of ∼24 h. This fundamental rhythm is also affected by the planet's slanted rotational axis, which causes seasonal variations in the length of the day. How life has adapted to anticipate this yearly rhythm is still debated.The suprachiasmatic nucleus (SCN), the central circadian (∼24 h) pacemaker in mammals, consists of ∼10,000 "clock" neurons. These single-cell clocks maintain endogenous rhythms by autoregulatory feedback loops of genes including period (Per) and brain and muscle Arnt-like 1 (Bmal1) (1). Although it was speculated that seasonal rhythms might be encoded in a single cell (2), single-cell oscillations remain similar regardless of the seasonal time that the SCN tissue encodes (3). Seasonal timing is thus proposed to be encoded in the network of the SCN (4-7) through spatial reorganization of the relative phases of clocks within individual cells (8-10). Subsets of SCN clocks form phase clusters (11) that map approximately to dorsal (shell, D-SCN) and ventral (core, V-SCN) regions of the SCN. When measured through a luciferase reporter monitoring oscillations in the Bmal1 gene, the D-SCN and V-SCN clusters show a phase gap, ...

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Section: Discussionmentioning

confidence: 99%

GABA-mediated repulsive coupling between circadian clock neurons in the SCN encodes seasonal time

Myung

Hong

DeWoskin

et al. 2015

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

146

229

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“…In the adult SCN samples we have used, there was little spatial jittering of neurons during culture (inset, second row) except for the first 24 h after preparation of culture. Heterogeneous phases of bioluminescence activities in SCN cultures have been observed using Per1 (Quintero et al, 2003;Yamaguchi et al, 2003) and Per2 reporter systems (Evans et al, 2011;Foley et al, 2011;Fukuda et al, 2011), which were previously interpreted as spatially propagating waves or tides that expand and recede back to their point of origin (Yan et al, 2007;Butler and Silver, 2009). …”

Section: Clustering Of Bmal1 Oscillatorsmentioning

confidence: 99%

Period Coding of Bmal1 Oscillators in the Suprachiasmatic Nucleus

Myung¹,

Hong

Hatanaka

et al. 2012

Journal of Neuroscience

121

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Together with computer simulations, we show that either the intercellular coupling does not strongly influence the Bmal1 oscillation or the nature of the coupling is more complex than previously assumed. Furthermore, we have found that the region-specific periods are modulated by the light conditions that an animal is exposed to. Based on these, we suggest that the period forms the basis of seasonal coding in the SCN.

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“…It is clear that SCN cells are a heterogenous population with distinct oscillatory properties [61,[70][71][72]. Computational models have predicted that inclusion of more damped oscillators or placement of damped oscillators at more highly connected hubs in the network can yield higher and faster synchrony [73][74][75][76][77][78].…”

Section: Suprachiasmatic Nucleus and The Synchrony Of Cellular Circadmentioning

confidence: 99%

Socially synchronized circadian oscillators

et al. 2013

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Daily rhythms of physiology and behaviour are governed by an endogenous timekeeping mechanism (a circadian 'clock'). The alternation of environmental light and darkness synchronizes (entrains) these rhythms to the natural day-night cycle, and underlying mechanisms have been investigated using singly housed animals in the laboratory. But, most species ordinarily would not live out their lives in such seclusion; in their natural habitats, they interact with other individuals, and some live in colonies with highly developed social structures requiring temporal synchronization. Social cues may thus be critical to the adaptive function of the circadian system, but elucidating their role and the responsible mechanisms has proven elusive. Here, we highlight three model systems that are now being applied to understanding the biology of socially synchronized circadian oscillators: the fruitfly, with its powerful array of molecular genetic tools; the honeybee, with its complex natural society and clear division of labour; and, at a different level of biological organization, the rodent suprachiasmatic nucleus, site of the brain's circadian clock, with its network of mutually coupled single-cell oscillators. Analyses at the 'group' level of circadian organization will likely generate a more complex, but ultimately more comprehensive, view of clocks and rhythms and their contribution to fitness in nature.

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Exploring Spatiotemporal Organization of SCN Circuits

Cited by 104 publications

References 123 publications

GABA-mediated repulsive coupling between circadian clock neurons in the SCN encodes seasonal time

GABA-mediated repulsive coupling between circadian clock neurons in the SCN encodes seasonal time

Period Coding of Bmal1 Oscillators in the Suprachiasmatic Nucleus

Socially synchronized circadian oscillators

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