A subset of ipRGCs regulates both maturation of the circadian clock and segregation of retinogeniculate projections in mice

Chew, Kylie S.; Renna, Jordan M.; McNeill, David S.; Fernandez, Diego C.; Keenan, William T; Thomsen, Michael B; Ecker, Jennifer L.; Loevinsohn, Gideon; VanDunk, Cassandra; Vicarel, Daniel C; Tufford, Adele; Weng, Shi-Jun; Gray, Paul A.; Cayouette, Michel; Herzog, Erik D.; Zhao, Haiqing; Berson, David M.; Hattar, Samer

doi:10.7554/elife.22861

Cited by 79 publications

(80 citation statements)

References 96 publications

(169 reference statements)

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“…As recently described (Chew et al, 2017; Prigge et al, 2016), this mouse line achieves a near-complete ablation of ipRGCs during development, with ipRGC axons failing to invade the suprachiasmatic nucleus, and it shows no changes in number and morphology of various retinal cell types (Chew et al, 2017). We observed no obvious changes in the lamination of bipolar cells (Figure S1A), amacrine cells (Figure S1B), RGCs (Figure S1C), rod photoreceptors (Figures S2A and S2B), or horizontal cells (Figure S2C) in Opn4 DTA/DTA retinas compared to wild-types.…”

Section: Resultssupporting

confidence: 52%

“…To test this idea, we ablated ipRGCs during development using animals expressing two copies of Diptheria-toxin A subunit in place of the melanopsin protein-coding locus ( Opn4 DTA/DTA ) (Chew et al, 2017). As recently described (Chew et al, 2017; Prigge et al, 2016), this mouse line achieves a near-complete ablation of ipRGCs during development, with ipRGC axons failing to invade the suprachiasmatic nucleus, and it shows no changes in number and morphology of various retinal cell types (Chew et al, 2017).…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, we demonstrate here a previously unsuspected role for light-evoked experience in the regulation of dendrite outgrowth, as evidenced by the changes in the number of melanopsin ORDs observed in DD animals. We cannot rule out the possibility that light may act via additional mechanisms to influence cone photoreceptor positioning during development, including but not limited to Opn5 /neuropsin-mediated photosensitivity (Buhr et al, 2015), or secondary effects of ipRGC silencing/light deprivation, such as altered retinal wave properties (Chew et al, 2017; Renna et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

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Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina

et al. 2018

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SUMMARY Newborn neurons follow molecular cues to reach their final destination, but whether early life experience influences lamination remains largely unexplored. As light is among the first stimuli to reach the developing nervous system via intrinsically photosensitive retinal ganglion cells (ipRGCs), we asked whether ipRGCs could affect lamination in the developing mouse retina. We show here that ablation of ipRGCs causes cone photoreceptors to mislocalize at different apicobasal positions in the retina. This effect is partly mediated by light-evoked activity in ipRGCs, as dark rearing or silencing of ipRGCs leads a subset of cones to mislocalize. Furthermore, ablation of ipRGCs alters the cone transcriptome and decreases expression of the dopamine receptor D4, while injection of L-DOPA or D4 receptor agonist rescues the displaced cone phenotype observed in dark-reared animals. These results show that early light-mediated activity in ipRGCs influences neuronal lamination and identify ipRGC-elicited dopamine release as a mechanism influencing cone position.

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Section: Resultssupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina

et al. 2018

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“…Prior to eye opening, light modulates critical developmental processes through a small population of retinal ganglion cells in the inner retina that express the photopigment melanopsin. Photic activation of melanopsin expressing retinal ganglion cells between P4 and P7 modulates retinal wave activity, a critical mechanism for the segregation of retinogeniculate projections into discrete ocular domains (1, 2). These waves of activity switch from cholinergic propagation (P1-P7) to glutamatergic propagation between P8 and P12, however, any light-mediated effect on glutamatergic waves remains uninvestigated (48-51).…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, studies in mice have shown that light can modulate retinal wave activity and assist in the segregation of retinogeniculate projections to discrete ocular domains even prior to eye opening at postnatal day 13 (P13) (1, 2). Other studies have shown that light can regulate vascular patterning in the retina (3) and can induce negative phototaxis in mice prior to eye opening (4).…”

Section: Introductionmentioning

confidence: 99%

The Development of Mid-Wavelength Photoresponsivity in the Mouse Retina

Bonezzi

Stabio

Renna

2018

Current Eye Research

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Purpose Photoreceptors in the mouse retina express much of the molecular machinery necessary for phototransduction and glutamatergic transmission prior to eye opening at postnatal day 13. Light responses have been observed collectively from rod and cone photoreceptors via electroretinogram recordings as early as postnatal day 13 (P13) in mouse, and the responses are known to become more robust with maturation, reaching a mature state by P30. Photocurrents from single rod outer segments have been recorded at P12, but no earlier, and similar studies on cone photoreceptors have been done, but only in the adult mouse retina. In this study, we wanted to document the earliest time point in which outer retinal photoreceptors in the mouse retina begin to respond to mid-wavelength light. Methods Ex-vivo electroretinogram recordings were made from isolated mouse retinae at P7, P8, P9, P10 and P30 at seven different flash energies (561 nm). The a-wave was pharmacologically isolated and measured at each developmental time point across all flash energies. Results Outer-retinal photoreceptors generated a detectable response to mid-wavelength light as early as P8, but only at photopic flash energies. A-wave intensity response curves and kinetic response properties are similar to the mature retina as early as P10. Conclusion These data represent the earliest recorded outer retinal light responses in the rodent. Photoreceptors are electrically functional and photoresponsive prior to eye opening, and much earlier than previously thought. Prior to eye opening, critical developmental processes occur that have been thought to be independent of outer retinal photic modulation. However, these data suggest light acting through outer-retinal photoreceptors has the potential to shape these critical developmental processes.

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Melanopsin ganglion cell outer retinal dendrites: Morphologically distinct and asymmetrically distributed in the mouse retina

Sondereker

Onyak

Islam

et al. 2017

J of Comparative Neurology

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A small population of retinal ganglion cells express the photopigment melanopsin and function as autonomous photoreceptors. They encode global luminance levels critical for light-mediated non-image forming visual processes including circadian rhythms and the pupillary light reflex. There are five melanopsin ganglion cell subtypes (M1–M5). M1 and displaced M1 (M1d) cells have dendrites that ramify within the outermost layer of the inner plexiform layer (IPL). It was recently discovered that some melanopsin ganglion cells extend dendrites into the outer retina. Outer Retinal Dendrites (ORDs) either ramify within the outer plexiform layer (OPL) or the inner nuclear layer (INL), and while present in the mature retina, are most abundant postnatally. Anatomical evidence for synaptic transmission between cone photoreceptor terminals and ORDs suggests a novel photoreceptor to ganglion cell connection in the mammalian retina. While it is known that the number of ORDs in the retina is developmentally regulated, little is known about the morphology, the cells from which they originate, or their spatial distribution throughout the retina. We analyzed the morphology of melanopsin-immunopositive ORDs in the OPL at different developmental time points in the mouse retina and identified five types of ORD originating from either M1 or M1d cells. However, a pattern emerges within these: ORDs from M1d cells are generally longer and more highly branched than ORDs from conventional M1 cells. Additionally, we found ORDs asymmetrically distributed to the dorsal retina. This morphological analysis provides the first step in identifying a potential role for biplexiform melanopsin ganglion cell ORDs.

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A subset of ipRGCs regulates both maturation of the circadian clock and segregation of retinogeniculate projections in mice

Cited by 79 publications

References 96 publications

Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina

Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina

The Development of Mid-Wavelength Photoresponsivity in the Mouse Retina

Melanopsin ganglion cell outer retinal dendrites: Morphologically distinct and asymmetrically distributed in the mouse retina

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