Heterogeneous Expression of the Core Circadian Clock Proteins among Neuronal Cell Types in Mouse Retina

Liu, Xiaoqin; Zhang, Zhijing; Ribelayga, Christophe

doi:10.1371/journal.pone.0050602

Cited by 61 publications

(101 citation statements)

References 52 publications

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“…The presence of a circadian component in the rod junctional conductance in the CBA/Ca strain and its absence in the C57BL/6 strain we report here are consistent with a key role for the melatonin/dopamine clock pathway in the control of photoreceptor coupling. The results are also consistent with the absence of an intrinsic circadian clock in the rods (Liu et al, 2012;McMahon et al, 2014) that would directly control rod function and further support the importance of neuromodulator rhythms in the control of rod coupling.…”

Section: Discussionsupporting

confidence: 75%

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Direct Evidence for Daily Plasticity of Electrical Coupling between Rod Photoreceptors in the Mammalian Retina

Jin

Ribelayga

2016

J. Neurosci.

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Rod photoreceptors are electrically coupled through gap junctions. Coupling is a key determinant of their light response properties, but whether rod electrical coupling is dynamically regulated remains elusive and controversial. Here, we have obtained direct measurements of the conductance between adjacent rods in mouse retina and present evidence that rod electrical coupling strength is dependent on the time of day, the lighting conditions, and the mouse strain. Specifically, we show in CBA/Ca mice that under circadian conditions, the rod junctional conductance has a median value of 98 pS during the subjective day and of 493 pS during the subjective night. In C57BL/6 mice, the median junctional conductance between dark-adapted rods is ϳ140 pS, regardless of the time in the circadian cycle. Adaptation to bright light decreases the rod junctional conductance to ϳ0 pS, regardless of the time of day or the mouse strain. Together, these results establish the high degree of plasticity of rod electrical coupling over the course of the day. Estimates of the rod coupling strength will provide a foundation for further investigations of rod interactions and the role of rod coupling in the ability of the visual system to anticipate, assimilate, and respond to the daily changes in ambient light intensity.

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Section: Discussionsupporting

confidence: 75%

“…Immunohistochemistry of cone arrestin was done as previously described (Liu et al, 2012). The primary antibody was a polyclonal rabbit anti-mouse cone arrestin antibody (Millipore Ab15282; 1/500).…”

mentioning

confidence: 99%

Direct Evidence for Daily Plasticity of Electrical Coupling between Rod Photoreceptors in the Mammalian Retina

Jin

Ribelayga

2016

J. Neurosci.

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“…However, attempts to identify the rhythm-generating cells of the retinal circadian clock have yielded conflicting results. Dopaminergic amacrine cells have been suggested as circadian pacemaker cells, as Per1 (10) and CRY2 (11) have been described as oscillating in these cells. Dopamine appears to act as a synchronizing signal for the retinal clock (12, 13).…”

mentioning

confidence: 99%

Differential roles for cryptochromes in the mammalian retinal clock

et al. 2018

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Cryptochromes 1 and 2 (CRY1/2) are key components of the negative limb of the mammalian circadian clock. Like many peripheral tissues, Cry1 and -2 are expressed in the retina, where they are thought to play a role in regulating rhythmic physiology. However, studies differ in consensus as to their localization and function, and CRY1 immunostaining has not been convincingly demonstrated in the retina. Here we describe the expression and function of CRY1 and -2 in the mouse retina in both sexes. Unexpectedly, we show that CRY1 is expressed throughout all retinal layers, whereas CRY2 is restricted to the photoreceptor layer. Retinal period 2::luciferase recordings from CRY1-deficient mice show reduced clock robustness and stability, while those from CRY2-deficient mice show normal, albeit long-period, rhythms. In functional studies, we then investigated well-defined rhythms in retinal physiology. Rhythms in the photopic electroretinogram, contrast sensitivity, and pupillary light response were all severely attenuated or abolished in CRY1-deficient mice. In contrast, these physiological rhythms are largely unaffected in mice lacking CRY2, and only photopic electroretinogram rhythms are affected. Together, our data suggest that CRY1 is an essential component of the mammalian retinal clock, whereas CRY2 has a more limited role.—Wong, J. C. Y., Smyllie, N. J., Banks, G. T., Pothecary, C. A., Barnard, A. R., Maywood, E. S., Jagannath, A., Hughes, S., van der Horst, G. T. J., MacLaren, R. E., Hankins, M. W., Hastings, M. H., Nolan, P. M., Foster, R. G., Peirson, S. N. Differential roles for cryptochromes in the mammalian retinal clock.

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“…50 Moreover, the cellular diversity of mammalian retina renders difficult the analysis of the circadian clock at the whole-tissue level because differences in phasing and period between cells/layers may result in low-amplitude rhythmicity or masking of coherent clock gene expression. 22,38,[51][52][53][54][55] It is therefore essential to determine which cell types possess clock properties to understand rhythm generation in the retina. Based on the molecular and physiological data from amphibians and birds, the initial prevailing model for circadian organization in vertebrate retinas proposed that photoreceptors contain self-sustained circadian clocks.…”

Section: Cellular and Layer Organization Of The Retinal Clock At The mentioning

confidence: 99%

“…Surprisingly, the authors came to the conclusion that, although clock proteins are present in most cell types besides rods, rhythmic expression is detected uniquely in cones. 53 Müller cells, the main glial cell type of the retina, have been demonstrated to also express sustained rhythms in primary culture of rodent or human cells transduced by luciferase-expressing viruses. 70 Taken together and in spite of some discrepancy, these data suggest that clock genes are expressed throughout the retina.…”

Section: Cellular and Layer Organization Of The Retinal Clock At The mentioning

confidence: 99%

The retinal clock in mammals: role in health and disease

Felder-Schmittbuhl¹,

Calligaro²,

Dkhissi-Benyahya³

2017

CPT

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Abstract:The mammalian retina contains an extraordinary diversity of cell types that are highly organized into precise circuits to perceive and process visual information in a dynamic manner and transmit it to the brain. Above this builds up another level of complex dynamic, orchestrated by a circadian clock located within the retina, which allows retinal physiology, and hence visual function, to adapt to daily changes in light intensity. The mammalian retina is a remarkable model of circadian clock because it harbors photoreception, self-sustained oscillator function, and physiological outputs within the same tissue. However, the location of the retinal clock in mammals has been a matter of long debate. Current data have shown that clock properties are widely distributed among retinal cells and that the retina is composed of a network of circadian clocks located within distinct cellular layers. Nevertheless, the identity of the major pacemaker, if any, still warrants identification. In addition, the retina coordinates rhythmic behavior by providing visual input to the master hypothalamic circadian clock in the suprachiasmatic nuclei (SCN). This light entrainment of the SCN to the light/dark cycle involves a network of retinal photoreceptor cells: rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Although it was considered that these photoreceptors synchronized both retinal and SCN clocks, new data challenge this view, suggesting that none of these photoreceptors is involved in photic entrainment of the retinal clock. Because circadian organization is a ubiquitous feature of the retina and controls fundamental processes, the coherence from cell to tissue is critical for circadian functions, and disruption of retinal clock organization or its response to light can potentially have a major impact on retinal pathophysiology and vision.

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Heterogeneous Expression of the Core Circadian Clock Proteins among Neuronal Cell Types in Mouse Retina

Cited by 61 publications

References 52 publications

Direct Evidence for Daily Plasticity of Electrical Coupling between Rod Photoreceptors in the Mammalian Retina

Direct Evidence for Daily Plasticity of Electrical Coupling between Rod Photoreceptors in the Mammalian Retina

Differential roles for cryptochromes in the mammalian retinal clock

The retinal clock in mammals: role in health and disease

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