Christophe P. Ribelayga

University of Houston | U of H, UH · College of Optometry Department of Vision Sciences

Purpose: The present study tested the hypothesis that connexin-36 (Cx36) and gap junctions between photoreceptor cells contribute to the circadian rhythm of the photopic electroretinogram (ERG) b-wave amplitude. Methods: Cone-specific disruption of Cx36 was obtained in mice with a floxed Gjd2 gene and human red/green pigment promoter (HRGP)-driv...

Mouse photoreceptors are electrically coupled via gap junctions, but the relative importance of rod/rod, cone/cone, or rod/cone coupling is unknown. Furthermore, while connexin36 (Cx36) is expressed by cones, the identity of the rod connexin has been controversial. We report that FACS-sorted rods and cones both express Cx36 but no other connexins....

Using serial blockface-scanning electron microscopy (SBF-SEM) and focused ion beam-scanning electron microscopy (FIB-SEM), combined with confocal microscopy for the gap junction protein Cx36, we reconstructed mouse photoreceptor terminals and located the gap junctions between them. An exuberant spray of fine telodendria extends from each cone pedic...

Significance The study of visual pigments (rhodopsin in rods and cone opsins in cones) in vision has a long and illustrious history. It is well established that rhodopsin is required for rod phototransduction, outer segment formation, and rod viability. It is not known if the same is true for the cones. By using the cone opsin–deficient mice, we ma...

In the retina, signals originating from rod and cone photoreceptors can reach retinal ganglion cells (RGCs)—the output neurons—through different pathways. However, little is known about the exact sensitivities and operating ranges of these pathways. Previously, we created rod- or cone-specific Cx36 knockout (KO) mouse lines. Both lines are deficien...

Circadian (24-h) clocks are cell-autonomous biological oscillators that orchestrate many aspects of our physiology on a daily basis. Numerous circadian rhythms in mammalian and non-mammalian retinas have been observed and the presence of an endogenous circadian clock has been demonstrated. However, how the clock and associated rhythms assemble into...

Article Divergent outer retinal circuits drive image and non-image visual behaviors Graphical abstract Highlights d The OFF pathway drives image-forming vision but not non-image-forming vision d Non-image-forming vision requires the most sensitive retinal pathway d The primary rod pathway is necessary and sufficient for the pupillary light response...

This project was inspired by the paper from Behrens et al (2016) who used e2006 to reconstruct bipolar cells. We thank Christian Behrens, Timm Schubert, Philipp Berens and Thomas Euler (University of Tübingen) for generously sharing data on blue cone bipolar cells. We thank Moritz Helmstaedter (MPI, Frankfurt) for hosting the e2006 dataset. We than...

Synaptic signaling complexes are held together by scaffold proteins, each of which is selectively capable of interacting with a number of other proteins. In previous studies of rabbit retina, we found Synapse-Associated Protein-102 (SAP102) and Channel Associated Protein of Synapse-110 (Chapsyn110) selectively localized in the tips of horizontal ce...

Adenosine, a major neuromodulator in the central nervous system (CNS), is involved in a variety of regulatory functions such as the sleep/wake cycle. Because exogenous adenosine displays dark-and night-mimicking effects in the vertebrate retina, we tested the hypothesis that a circadian (24 h) clock in the retina uses adenosine to control neuronal...

Outer retinal circuits that drive non-image forming vision in mammals are unknown. Rods and cones signal light increments and decrements to the brain through the ON and OFF pathways, respectively. Although their contribution to image-forming vision is known, the contributions of the ON and OFF pathway to the pupillary light response (PLR), a non-im...

BMAL1 is a core component of the mammalian circadian clockwork. Removal of BMAL1 from the retina significantly affects visual information processing in both rod and cone pathways. To identify potential pathways and/or molecules through which BMAL1 alters signal transmission at the cone pedicle, we performed an RNA‐seq differential expression analys...

Every day and night, the retina undergoes dramatic changes in its physiology and function. The prevailing view is that these daily changes affect the retinal output and thereby visual perception. Recent evidence suggests that modifications in higher-order processing centers, and not in retinal computations, account for variations in visual sensitiv...

Gap junction-mediated electrical coupling between retinal photoreceptors is an important determinant of photoreceptor function. Yet, quantitative measurements of the junctional conductance between coupled photoreceptors are required to fully assess the effects of coupling on visual performance. Such measurements have been obtained in salamander and...

Although it is well established that the vertebrate retina contains endogenous circadian clocks that regulate retinal physiology and function during day and night, the processes that the clocks affect and the means by which the clocks control these processes remain unresolved. We previously demonstrated that a circadian clock in the goldfish retina...

Vision is a highly rhythmic function adapted to the extensive changes in light intensity occurring over the 24-hour day. This adaptation relies on rhythms in cellular and molecular processes, which are orchestrated by a network of circadian clocks located within the retina and in the eye, synchronized to the day/night cycle and which, together, fin...

The C57BL/6J (B6) is the most common inbred mouse strain used in biomedical research in the United States. Yet, this strain is notoriously known for being deficient in the biosynthesis of melatonin, an important effector of circadian clocks in the brain and in the retina. Melatonin deficiency in this strain results from non‐functional alleles of th...

Circadian rhythms are present in most living organisms, and these rhythms are not just a consequence of the day/night fluctuation, but rather they are generated by endogenous biological clocks with a periodicity of about 24 h. In mammals, the master pacemaker of circadian rhythms is localized in the suprachiasmatic nuclei (SCN) of the hypothalamus....

In the retina, electrical coupling through gap junctions is present in all major classes of neurons. Electrical coupling in the retina was first reported more than four decades ago and great strides have been made in understanding its properties and roles. It has become clear that dynamic modulation of electrical coupling is a critical element of c...

Dopamine is a key neurotransmitter in the retina and plays a central role in the light adaptive processes of the visual system. The sole source of retinal dopamine is dopaminergic amacrine cells (DACs). We and others have previously demonstrated that DACs are activated by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs)...

Purpose: Retinal dopamine deficiency is a potential cause of myopia and visual deficits in retinopathy of prematurity (ROP). We investigated the cellular mechanisms responsible for lowered levels of retinal dopamine in an oxygen-induced retinopathy (OIR) mouse model of ROP. Methods: Retinopathy was induced by exposing mice to 75% oxygen from pos...

Unlabelled: 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 pres...

The gap-junction-forming protein connexin36 (Cx36) represents the anatomical substrate of photoreceptor electrical coupling in mammals. The strength of coupling is directly correlated to the phosphorylation of Cx36 at two regulatory sites: Ser110 and Ser293. Our previous work demonstrated that the extent of biotinylated tracer coupling between phot...

Rod single-photon responses are critical for vision in dim light. Electrical coupling via gap junction channels shapes the light response properties of vertebrate photoreceptors, but the regulation of rod coupling and its impact on the single-photon response have remained unclear. To directly address these questions, we developed a perforated patch...

Opsin 4 (Opn4)/melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) play a major role in non-image-forming visual system. Although advances have been made in understanding their morphological features and functions, the molecular mechanisms that regulate their formation and survival remain unknown. Previously, we found...

Rod photoreceptors play a critical role for vision under dim light by providing the reliable detection and transmission of single photons. Phototransduction current in the rod outer segment and photocurrent from electrically coupled neighboring rods are central processes that shape the rod photovoltage in vertebrates in general. However, in mammals...

In mammalian retina, the non-image-forming visual system is composed of the melanopsin/Opn4-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). IpRGCs were discovered as a third type of photoreceptors primarily involved in conveying tasks such as circadian photo-entrainment and pupillary light reflex (PLR). Despite a wealth of...

Gap junctions in retinal photoreceptors suppress voltage noise and facilitate input of rod signals into the cone pathway during mesopic vision. These synapses are highly plastic and regulated by light and circadian clocks. Recent studies have revealed an important role for connexin36 (Cx36) phosphorylation by protein kinase A (PKA) in regulating ce...

Circadian rhythms in metabolism, physiology, and behavior originate from cell-autonomous circadian clocks located in many organs and structures throughout the body and that share a common molecular mechanism based on the clock genes and their protein products. In the mammalian neural retina, despite evidence supporting the presence of several circa...

Purpose: Ganglion cells (GCs) display a center-surround receptive field (RF) following prolonged (>30 min) light adaptation, but exhibit minimal surrounds following prolonged dark adaptation (Barlow et al., 1957). Bipolar cell (BC) surround strength also decreases when the background illumination is reduced (Fahey & Burkhardt, 2003). Under light-ad...

In addition to chemical synaptic transmission, neurons that are connected by gap junctions can also communicate rapidly via electrical synaptic transmission. Increasing evidence indicates that gap junctions not only permit electrical current flow and synchronous activity between interconnected or coupled cells, but that the strength or effectivenes...

Ganglion cells (GCs) display a center-surround receptive field (RF) following prolonged (>30 min) light adaptation, but lose their surround responses following prolonged dark adaptation (Barlow et al., 1957). Bipolar cell (BC) surround strength also decreases when the intensity of background illumination is reduced (Fahey & Burkhardt, 2001). Under...

Most vertebrate retinas have both rod and cone photoreceptor cells. Based primarily on electrical recordings of dissociated rods and cones, it has been accepted that rods operate at low light levels at night and cones operate at high light levels in the day. Recent evidence, however, demonstrates that cones in the intact retina respond to very dim...

Although the circadian clock in the mammalian retina regulates many physiological processes in the retina, it is not known whether and how the clock controls the neuronal pathways involved in visual processing. By recording the light responses of rabbit axonless (A-type) horizontal cells under dark-adapted conditions in both the day and night, we f...

The recent discovery of the critical role of TRPM1 in retinal function in vertebrates has come as a surprise and has already provided important insights into a common cause of blindness.

Although rod and cone photoreceptor cells in the vertebrate retina are anatomically connected or coupled by gap junctions, a type of electrical synapse, rod-cone electrical coupling is thought to be weak. Using tracer labeling and electrical recording in the goldfish retina and tracer labeling in the mouse retina, we show that the retinal circadian...

Horizontal cells are second order neurons that receive direct synaptic input from photoreceptors. In teleosts horizontal cells can be divided into two categories, cone-connected and rod-connected. Although the anatomy and physiology of fish cone horizontal cells have been extensively investigated, less is known about rod horizontal cells. This stud...

Like nocturnal rodents, the diurnal tropical rodent Arvicanthis ansorgei shows a daily rhythm in pineal melatonin content. Seasonal and photoperiodic variations in the biosynthetic activity of the pineal gland: arylalkylamine-N-acetyltransferase (AA-NAT), hydroxyindole-O-methyltransferase (HIOMT) activities and melatonin content were measured in ma...

Although the purine adenosine acts as an extracellular neuromodulator in the mammalian CNS in both normal and pathological conditions and regulates sleep, the regulation of extracellular adenosine in the day and night is incompletely understood. To determine how extracellular adenosine is regulated, rabbit neural retinas were maintained by superfus...

Although many biochemical, morphological and physiological processes in the vertebrate retina are controlled by a circadian (24 h) clock, the location of the clock and how the clock alters retinal function are unclear. For instance, several observations have suggested that dopamine, a retinal neuromodulator, may play an important role in retinal rh...

In fish and other vertebrate retinas, although dopamine release is regulated by both light and an endogenous circadian (24-hour) clock, light increases dopamine release to a greater extent than the clock. The clock increases dopamine release during the subjective day so that D2-like receptors are activated. It is not known, however, whether the ret...

Melatonin, the major hormone produced by the pineal gland, displays characteristic daily and seasonal patterns of secretion. These robust and predictable rhythms in circulating melatonin are strong synchronizers for the expression of numerous physiological processes in photoperiodic species. In mammals, the nighttime production of melatonin is main...

In the Syrian hamster, the role of noradrenaline in the regulation of melatonin synthesis is less clear than in the rat. During pineal ontogenesis in the rat, noradrenaline is the major transmitter involved in the onset of melatonin synthesis and melatonin rhythm. We analysed the involvement of noradrenaline in the ontogenesis of melatonin synthesi...

A circadian (24-hour) clock regulates the light responses of fish cone horizontal cells, second order neurones in the retina that receive synaptic contact from cones and not from rods. Due to the action of the clock, cone horizontal cells are driven by cones in the day, but primarily driven by rods at night. We show here that dopamine, a retinal ne...

Zinc is strikingly co-localized with glutamate-containing vesicles in the synaptic terminals of retinal photoreceptors, and it is thought to be co-released with glutamate onto postsynaptic neurons such as horizontal cells and bipolar cells. Here we examined exogenous zinc modulation of glutamate receptors on cultured retinal horizontal cells using...

The time giver hormone melatonin is secreted with both daily and seasonal rhythms in the mammalian pineal gland. We report here that the two main melatoninsynthesizing enzymes N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) are differently involved in the regulation of the daily and photoperiodic rhythms of melatonin synthes...

Zinc is strikingly co-localized with glutamate-containing vesicles in the synaptic terminals of retinal photoreceptors, and it is thought to be co-released with glutamate onto postsynaptic neurons such as horizontal cells and bipolar cells. Here we examined exogenous zinc modulation of glutamate receptors on cultured retinal horizontal cells using...

In the pineal, melatonin (Mel) is synthesized from serotonin by arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT). Although it is clear that AA-NAT drives the daily rhythm in Mel synthesis, the mechanisms involved in the photoperiodic changes of the amplitude of the Mel peak, as observed in the Siberian hamst...

Photoperiodic changes of pineal melatonin (MEL) profile are accompanied by parallel changes of arylalkylamine-N-acetyltransferase (AA-NAT) activity. In the present study, the authors investigated, for the first time, whether two other important variables of pineal metabolism, AA-NAT and hydroxyindole-O-methyltransferase (HIOMT) gene expression, als...

In the pineal gland, synthesis of melatonin requires O-methylation catalyzed by hydroxyindole-O-methyltransferase (HIOMT; EC 2.1.1.4). We investigated in vivo the molecular mechanisms involved in the regulation of rat pineal HIOMT messenger RNA (mRNA) expression and activity using in situ hybridization and radioenzymatic assay. HIOMT mRNA levels an...

In the pineal gland, synthesis of melatonin requires O-methylation catalyzed by hydroxyindole-O-methyltransferase (HIOMT; EC 2.1.1.4). We investigated in vivo the molecular mechanisms involved in the regulation of rat pineal HIOMT messenger RNA (mRNA) expression and activity using in situ hybridization and radioenzymatic assay. HIOMT mRNA levels an...

Postnatal development of hydroxyindole-O-methyltransferase (HIOMT) mRNA expression, HIOMT activity and melatonin content was investigated in the rat pineal gland from birth to adulthood (62-day old). For each age, animals were sacrificed at two different time-points: midday and midnight. HIOMT mRNA was first detectable one day after birth and maxim...

Hydroxyindole-O-methyltransferase (HIOMT) catalyses the last step of all the 5-methoxyindoles synthesized in the pineal gland. The synthetic activity of this neuroendocrine structure is driven not only by noradrenaline but also by various neuropeptides. Recently we have established (1) that one of these neuropeptides, neuropeptide Y (NPY), stimulat...

Hydroxyindole-O-methyltransferase (HIOMT) is the enzyme involved in the last step of the melatonin synthesis pathway. Recently, a cDNA encoding HIOMT has been isolated from a rat pineal gland library. Using this cDNA, we developed a highly sensitive in situ hybridisation protocol to investigate the distribution of HIOMT mRNA in both the rat brain a...

Mechanisms involved in the regulation of hydroxyindole-O-methyltransferase (HIOMT) activity were investigated in the rat pineal. Isoproterenol, db-cAMP, PACAP or VIP had no acute (6 h) effect whereas NPY, thapsigargin and a PKC activator stimulated HIOMT activity by 30-40%. Chronic stimulation (6 days) with isoproterenol, db-cAMP, or each peptide p...