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1.
Nat Rev Neurosci ; 25(3): 159-175, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38279030

RESUMO

Ever-present in our environments, light entrains circadian rhythms over long timescales, influencing daily activity patterns, health and performance. Increasing evidence indicates that light also acts independently of the circadian system to directly impact physiology and behaviour, including cognition. Exposure to light stimulates brain areas involved in cognition and appears to improve a broad range of cognitive functions. However, the extent of these effects and their mechanisms are unknown. Intrinsically photosensitive retinal ganglion cells (ipRGCs) have emerged as the primary conduit through which light impacts non-image-forming behaviours and are a prime candidate for mediating the direct effects of light on cognition. Here, we review the current state of understanding of these effects in humans and mice, and the tools available to uncover circuit-level and photoreceptor-specific mechanisms. We also address current barriers to progress in this area. Current and future efforts to unravel the circuits through which light influences cognitive functions may inform the tailoring of lighting landscapes to optimize health and cognitive function.


Assuntos
Encéfalo , Células Ganglionares da Retina , Humanos , Camundongos , Animais , Células Ganglionares da Retina/fisiologia , Ritmo Circadiano/fisiologia , Cognição
2.
PLoS Biol ; 22(3): e3002535, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38470868

RESUMO

Light enables vision and exerts widespread effects on physiology and behavior, including regulating circadian rhythms, sleep, hormone synthesis, affective state, and cognitive processes. Appropriate lighting in animal facilities may support welfare and ensure that animals enter experiments in an appropriate physiological and behavioral state. Furthermore, proper consideration of light during experimentation is important both when it is explicitly employed as an independent variable and as a general feature of the environment. This Consensus View discusses metrics to use for the quantification of light appropriate for nonhuman mammals and their application to improve animal welfare and the quality of animal research. It provides methods for measuring these metrics, practical guidance for their implementation in husbandry and experimentation, and quantitative guidance on appropriate light exposure for laboratory mammals. The guidance provided has the potential to improve data quality and contribute to reduction and refinement, helping to ensure more ethical animal use.


Assuntos
Experimentação Animal , Animais de Laboratório , Animais , Reprodutibilidade dos Testes , Ritmo Circadiano/fisiologia , Mamíferos
3.
J Neurosci ; 42(20): 4101-4115, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35396331

RESUMO

Aversive responses to bright light (photoaversion) require signaling from the eye to the brain. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) encode absolute light intensity and are thought to provide the light signals for photoaversion. Consistent with this, neonatal mice exhibit photoaversion before the developmental onset of image vision, and melanopsin deletion abolishes photoaversion in neonates. It is not well understood how the population of ipRGCs, which constitutes multiple physiologically distinct types (denoted M1-M6 in mouse), encodes light stimuli to produce an aversive response. Here, we provide several lines of evidence that M1 ipRGCs that lack the Brn3b transcription factor drive photoaversion in neonatal mice. First, neonatal mice lacking TRPC6 and TRPC7 ion channels failed to turn away from bright light, while two photon Ca2+ imaging of their acutely isolated retinas revealed reduced photosensitivity in M1 ipRGCs, but not other ipRGC types. Second, mice in which all ipRGC types except for Brn3b-negative M1 ipRGCs are ablated exhibited normal photoaversion. Third, pharmacological blockade or genetic knockout of gap junction channels expressed by ipRGCs, which reduces the light sensitivity of M2-M6 ipRGCs in the neonatal retina, had small effects on photoaversion only at the brightest light intensities. Finally, M1s were not strongly depolarized by spontaneous retinal waves, a robust source of activity in the developing retina that depolarizes all other ipRGC types. M1s therefore constitute a separate information channel between the neonatal retina and brain that could ensure behavioral responses to light but not spontaneous retinal waves.SIGNIFICANCE STATEMENT At an early stage of development, before the maturation of photoreceptor input to the retina, neonatal mice exhibit photoaversion. On exposure to bright light, they turn away and emit ultrasonic vocalizations, a cue to their parents to return them to the nest. Neonatal photoaversion is mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs), a small percentage of the retinal ganglion cell population that express the photopigment melanopsin and depolarize directly in response to light. This study shows that photoaversion is mediated by a subset of ipRGCs, called M1-ipRGCs. Moreover, M1-ipRGCs have reduced responses to retinal waves, providing a mechanism by which the mouse distinguishes light stimulation from developmental patterns of spontaneous activity.


Assuntos
Retina , Opsinas de Bastonetes , Animais , Animais Recém-Nascidos , Junções Comunicantes , Camundongos , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/genética , Visão Ocular
4.
Cell Mol Life Sci ; 78(3): 889-907, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32965515

RESUMO

The melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) are a relatively recently discovered class of atypical ganglion cell photoreceptor. These ipRGCs are a morphologically and physiologically heterogeneous population that project widely throughout the brain and mediate a wide array of visual functions ranging from photoentrainment of our circadian rhythms, to driving the pupillary light reflex to improve visual function, to modulating our mood, alertness, learning, sleep/wakefulness, regulation of body temperature, and even our visual perception. The presence of melanopsin as a unique molecular signature of ipRGCs has allowed for the development of a vast array of molecular and genetic tools to study ipRGC circuits. Given the emerging complexity of this system, this review will provide an overview of the genetic tools and methods used to study ipRGCs, how these tools have been used to dissect their role in a variety of visual circuits and behaviors in mice, and identify important directions for future study.


Assuntos
Retina/metabolismo , Células Ganglionares da Retina/metabolismo , Opsinas de Bastonetes/metabolismo , Animais , Animais Geneticamente Modificados/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/ultraestrutura , Opsinas de Bastonetes/genética , Canais de Cátion TRPC/metabolismo , Fator de Transcrição Brn-3B/genética , Fator de Transcrição Brn-3B/metabolismo , Fosfolipases Tipo C/metabolismo , Vias Visuais/fisiologia
5.
J Exp Biol ; 224(23)2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34842918

RESUMO

Melanopsin is a visual pigment that is expressed in a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs). It is involved in regulating non-image forming visual behaviors, such as circadian photoentrainment and the pupillary light reflex, while also playing a role in many aspects of image-forming vision, such as contrast sensitivity. Melanopsin was initially discovered in the melanophores of the skin of the frog Xenopus, and subsequently found in a subset of ganglion cells in rat, mouse and primate retinas. ipRGCs were initially thought to be a single retinal ganglion cell population, and melanopsin was thought to activate a single, invertebrate-like Gq/transient receptor potential canonical (TRPC)-based phototransduction cascade within these cells. However, in the 20 years since the discovery of melanopsin, our knowledge of this visual pigment and ipRGCs has expanded dramatically. Six ipRGC subtypes have now been identified in the mouse, each with unique morphological, physiological and functional properties. Multiple subtypes have also been identified in other species, suggesting that this cell type diversity is a general feature of the ipRGC system. This diversity has led to a renewed interest in melanopsin phototransduction that may not follow the canonical Gq/TRPC cascade in the mouse or in the plethora of other organisms that express the melanopsin photopigment. In this Review, we discuss recent findings and discoveries that have challenged the prevailing view of melanopsin phototransduction as a single pathway that influences solely non-image forming functions.


Assuntos
Transdução de Sinal Luminoso , Opsinas de Bastonetes , Animais , Camundongos , Ratos , Retina , Células Ganglionares da Retina
6.
bioRxiv ; 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38559003

RESUMO

Altered function of peripheral sensory neurons is an emerging mechanism for symptoms of autism spectrum disorders. Visual sensitivities are common in autism, but whether differences in the retina might underlie these sensitivities is not well-understood. We explored retinal function in the Fmr1 knockout model of Fragile X syndrome, focusing on a specific type of retinal neuron, the "sustained On alpha" retinal ganglion cell. We found that these cells exhibit changes in dendritic structure and dampened responses to light in the Fmr1 knockout. We show that decreased light sensitivity is due to increased inhibitory input and reduced E-I balance. The change in E-I balance supports maintenance of circuit excitability similar to what has been observed in cortex. These results show that loss of Fmr1 in the mouse retina affects sensory function of one retinal neuron type. Our findings suggest that the retina may be relevant for understanding visual function in Fragile X syndrome.

7.
Sci Rep ; 14(1): 12499, 2024 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822033

RESUMO

In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual information-induced fear, and triggers a response. Looming-evoked behavior in rodents, mimicking response to aerial predators, allowed identify the neural circuitry underlying instinctive defensive behaviors; however, the influence of disk/background contrast on the looming-induced behavioral response has not been examined, either in rats or mice. We studied the influence of the dark disk/gray background contrast in the type of rat and mouse defensive behavior in the looming arena, and we showed that rat and mouse response as a function of disk/background contrast adjusted to a sigmoid-like relationship. Both sex and age biased the contrast-dependent response, which was dampened in rats submitted to retinal unilateral or bilateral ischemia. Moreover, using genetically manipulated mice, we showed that the three type of photoresponsive retinal cells (i.e., cones, rods, and intrinsically photoresponsive retinal ganglion cells (ipRGCs)), participate in the contrast-dependent response, following this hierarchy: cones > > rods > > > ipRGCs. The cone and rod involvement was confirmed using a mouse model of unilateral non-exudative age-related macular degeneration, which only damages canonical photoreceptors and significantly decreased the contrast sensitivity in the looming arena.


Assuntos
Estimulação Luminosa , Células Ganglionares da Retina , Animais , Ratos , Camundongos , Masculino , Células Ganglionares da Retina/fisiologia , Feminino , Sensibilidades de Contraste/fisiologia , Comportamento Animal/fisiologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Camundongos Endogâmicos C57BL , Percepção Visual/fisiologia , Medo/fisiologia , Retina/fisiologia , Vias Visuais/fisiologia
8.
bioRxiv ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38496475

RESUMO

In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual information-induced fear, and triggers a response. Looming-evoked behavior in rodents, mimicking response to aerial predators, allowed identify the neural circuitry underlying instinctive defensive behaviors; however, the influence of disk/background contrast on the looming-induced behavioral response has not been examined, either in rats or mice. We studied the influence of the dark disk/gray background contrast in the type of rat and mouse defensive behavior in the looming arena, and we showed that rat and mouse response as a function of disk/background contrast adjusted to a sigmoid-like relationship. Both sex and age biased the contrast-dependent response, which was dampened in rats submitted to retinal unilateral or bilateral ischemia. Moreover, using genetically manipulated mice, we showed that the three type of photoresponsive retinal cells (i.e., cones, rods, and intrinsically photoresponsive retinal ganglion cells (ipRGCs)), participate in the contrast-dependent response, following this hierarchy: cones ˃> rods ˃>>ipRGCs. The cone and rod involvement was confirmed using a mouse model of unilateral non-exudative age-related macular degeneration, which only damages canonical photoreceptors and significantly decreased the contrast sensitivity in the looming arena.

9.
bioRxiv ; 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38712084

RESUMO

The melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) comprise a subset of the ∼40 retinal ganglion cell types in the mouse retina and drive a diverse array of light-evoked behaviors from circadian photoentrainment to pupil constriction to contrast sensitivity for visual perception. Central to the ability of ipRGCs to control this diverse array of behaviors is the distinct complement of morphophysiological features and gene expression patterns found in the M1-M6 ipRGC subtypes. However, the genetic regulatory programs that give rise to subtypes of ipRGCs are unknown. Here, we identify the transcription factor Brn3b (Pou4f2) as a key genetic regulator that shapes the unique functions of ipRGC subtypes and their diverse downstream visual behaviors.

10.
Elife ; 122023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37937828

RESUMO

Melanopsin signaling within intrinsically photosensitive retinal ganglion cell (ipRGC) subtypes impacts a broad range of behaviors from circadian photoentrainment to conscious visual perception. Yet, how melanopsin phototransduction within M1-M6 ipRGC subtypes impacts cellular signaling to drive diverse behaviors is still largely unresolved. The identity of the phototransduction channels in each subtype is key to understanding this central question but has remained controversial. In this study, we resolve two opposing models of M4 phototransduction, demonstrating that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are dispensable for this process and providing support for a pathway involving melanopsin-dependent potassium channel closure and canonical transient receptor potential (TRPC) channel opening. Surprisingly, we find that HCN channels are likewise dispensable for M2 phototransduction, contradicting the current model. We instead show that M2 phototransduction requires TRPC channels in conjunction with T-type voltage-gated calcium channels, identifying a novel melanopsin phototransduction target. Collectively, this work resolves key discrepancies in our understanding of ipRGC phototransduction pathways in multiple subtypes and adds to mounting evidence that ipRGC subtypes employ diverse phototransduction cascades to fine-tune cellular responses for downstream behaviors.


Assuntos
Transdução de Sinal Luminoso , Células Ganglionares da Retina , Opsinas de Bastonetes , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Transdução de Sinal Luminoso/fisiologia , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/metabolismo , Visão Ocular , Animais , Camundongos
11.
J Neurosci ; 31(45): 16094-101, 2011 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-22072661

RESUMO

Melanopsin imparts an intrinsic photosensitivity to a subclass of retinal ganglion cells (ipRGCs). Generally thought of as irradiance detectors, ipRGCs target numerous brain regions involved in non-image-forming vision. ipRGCs integrate their intrinsic, melanopsin-mediated light information with rod/cone signals relayed via synaptic connections to influence light-dependent behaviors. Early observations indicated diversity among these cells and recently several specific subtypes have been identified. These subtypes differ in morphological and physiological form, controlling separate functions that range from biological rhythm via circadian photoentrainment, to protective behavioral responses including pupil constriction and light avoidance, and even image-forming vision. In this Mini-Symposium review, we will discuss some recent findings that highlight the diversity in both form and function of these recently discovered atypical photoreceptors.


Assuntos
Aprendizagem da Esquiva/fisiologia , Transdução de Sinal Luminoso/fisiologia , Células Ganglionares da Retina/metabolismo , Opsinas de Bastonetes/metabolismo , Animais , Humanos , Luz/efeitos adversos , Rede Nervosa/fisiologia , Células Fotorreceptoras/fisiologia , Células Ganglionares da Retina/classificação , Células Ganglionares da Retina/citologia , Vias Visuais
12.
J Neurosci ; 30(48): 16262-71, 2010 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-21123572

RESUMO

A small subset of ganglion cells in the mammalian retina express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). These cells are the primary conduits through which photic information is relayed to non-image-forming visual centers that mediate behaviors such as the pupillary light reflex and circadian entrainment. M1 and M2 cells comprise distinct morphological subpopulations of ipRGC, and possess physiological diversity in their intrinsic membrane properties and intrinsic light responses. Additionally, evidence now indicates that all ipRGCs receive photic information from rods/cones via synaptic signaling. It has recently been reported that Off-stratifying M1 cells paradoxically receive input from the On pathway within the Off sublamina of the inner plexiform layer. The purpose of the current study was to examine the functional consequences of cone pathway signaling to M1 and M2 cells. Using pharmacological tools and single-cell recordings of synaptic responses in wild-type and melanopsin-null mice, we found that the On pathway forms the primary excitatory synaptic input to both M1 and M2 cells. This input was much more influential in shaping the light-evoked responses and resting membrane properties of M2 cells than M1 cells. These findings indicate a surprising differential reliance upon cone-mediated phototransduction by ipRGC subpopulations. These findings also suggest that ipRGC subtypes signal diverse photic information to various non-image-forming visual centers.


Assuntos
Estimulação Luminosa/métodos , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Ganglionares da Retina/fisiologia , Animais , Animais Recém-Nascidos , Camundongos , Camundongos Knockout , Células Fotorreceptoras Retinianas Cones/citologia , Células Ganglionares da Retina/citologia , Opsinas de Bastonetes/deficiência , Opsinas de Bastonetes/genética
13.
Eur J Neurosci ; 33(5): 856-67, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21261756

RESUMO

In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate various non-image-forming photic responses, such as circadian photoentrainment, pupillary light reflex and pineal melatonin suppression. ipRGCs directly respond to environmental light by activation of the photopigment melanopsin followed by the opening of an unidentified cation-selective channel. Studies in heterologous expression systems and in the native retina have strongly implicated diacylglycerol-sensitive transient receptor potential channels containing TRPC3, TRPC6 and TRPC7 subunits in melanopsin-evoked depolarization. Here we show that melanopsin-evoked electrical responses largely persist in ipRGCs recorded from early postnatal (P6-P8) and adult (P22-P50) mice lacking expression of functional TRPC3, TRPC6 or TRPC7 subunits. Multielectrode array (MEA) recordings performed at P6-P8 stages under conditions that prevent influences from rod/cone photoreceptors show comparable light sensitivity for the melanopsin-evoked responses in these mutant mouse lines in comparison to wild-type (WT) mice. Patch-clamp recordings from adult mouse ipRGCs lacking TRPC3 or TRPC7 subunits show intrinsic light-evoked responses equivalent to those recorded in WT mice. Persistence of intrinsic light-evoked responses was also noted in ipRGCs lacking TRPC6 subunits, although with significantly smaller magnitudes. These results demonstrate that the melanopsin-evoked depolarization in ipRGCs is not mediated by either TRPC3, TRPC6 or TRPC7 channel subunits alone. They also suggest that the melanopsin signaling pathway includes TRPC6-containing heteromeric channels in mature retinas.


Assuntos
Diglicerídeos/metabolismo , Transdução de Sinal Luminoso/fisiologia , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/metabolismo , Canais de Cátion TRPC/metabolismo , Animais , Humanos , Luz , Camundongos , Camundongos Knockout , Técnicas de Patch-Clamp , Estimulação Luminosa , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Células Ganglionares da Retina/citologia , Canais de Cátion TRPC/genética , Canal de Cátion TRPC6
14.
J Neurosci ; 29(2): 476-82, 2009 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-19144848

RESUMO

A subset of ganglion cells in the mammalian retina express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). These cells are implicated in non-image-forming visual responses to environmental light, such as the pupillary light reflex, seasonal adaptations in physiology, photic inhibition of nocturnal melatonin release, and modulation of sleep, alertness, and activity. Morphological studies have confirmed the existence of at least three distinct subpopulations of ipRGCs, but studies of the physiology of ipRGCs at the single cell level have focused mainly on M1 cells, the dendrites of which stratify solely in sublamina a (OFF sublamina) of the retinal inner plexiform layer (IPL). Little work has been done to compare the functional properties of M1 cells to those of M2 cells, the dendrites of which stratify solely in sublamina b (ON sublamina) of the IPL. The goal of the current study was to compare the morphology, intrinsic light response, and intrinsic membrane properties of M1 and M2 cells in the mouse retina. Here we demonstrate additional morphological differences between M1 and M2 cells as well as distinct physiological characteristics of both the intrinsic light responses and intrinsic membrane properties. M2 cells displayed a more complex dendritic arborization and higher input resistance, yet showed lower light sensitivity and lower maximal light responses than M1 cells. These data indicate morphological and functional heterogeneity among ipRGCs.


Assuntos
Potenciais da Membrana/fisiologia , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/fisiologia , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Células Cultivadas , Colina O-Acetiltransferase/metabolismo , Dendritos/fisiologia , Estimulação Elétrica/métodos , Proteínas de Fluorescência Verde/genética , Técnicas In Vitro , Potenciais da Membrana/genética , Camundongos , Camundongos Transgênicos , Técnicas de Patch-Clamp , Estimulação Luminosa , Retina/citologia , Células Ganglionares da Retina/classificação , Opsinas de Bastonetes/genética , Vias Visuais/fisiologia
15.
J Comp Neurol ; 528(6): 1028-1040, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31691279

RESUMO

Multiple retinal ganglion cell (RGC) types in the mouse retina mediate pattern vision by responding to specific features of the visual scene. The M4 and M5 melanopsin-expressing, intrinsically photosensitive retinal ganglion cell (ipRGC) subtypes are two RGC types that are thought to play major roles in pattern vision. The M4 ipRGCs overlap in population with ON-alpha RGCs, while M5 ipRGCs were recently reported to exhibit opponent responses to different wavelengths of light (color opponency). Despite their seemingly distinct roles in visual processing, previous reports have suggested that these two populations may exhibit overlap in their morphological and functional properties, which calls into question whether these are in fact distinct RGC types. Here, we show that M4 and M5 ipRGCs are distinct morphological classes of ipRGCs, but they cannot be exclusively differentiated based on color opponency and dendritic morphology as previously reported. Instead, we find that M4 and M5 ipRGCs can only be distinguished based on soma size and the number of dendritic branch points in combination with SMI-32 immunoreactivity. These results have important implications for clearly defining RGC types and their roles in visual behavior.


Assuntos
Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/fisiologia , Animais , Feminino , Masculino , Camundongos
16.
Science ; 368(6490): 527-531, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32355031

RESUMO

Retinal ganglion cells (RGCs) drive diverse, light-evoked behaviors that range from conscious visual perception to subconscious, non-image-forming behaviors. It is thought that RGCs primarily drive these functions through the release of the excitatory neurotransmitter glutamate. We identified a subset of melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs) in mice that release the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at non-image-forming brain targets. GABA release from ipRGCs dampened the sensitivity of both the pupillary light reflex and circadian photoentrainment, thereby shifting the dynamic range of these behaviors to higher light levels. Our results identify an inhibitory RGC population in the retina and provide a circuit-level mechanism that contributes to the relative insensitivity of non-image-forming behaviors at low light levels.


Assuntos
Vias Neurais/fisiologia , Células Ganglionares da Retina/fisiologia , Percepção Visual/fisiologia , Animais , Feminino , Neurônios GABAérgicos/fisiologia , Glutamato Descarboxilase/metabolismo , Luz , Masculino , Camundongos , Camundongos Mutantes , Vias Neurais/efeitos dos fármacos , Reflexo Pupilar/fisiologia , Reflexo Pupilar/efeitos da radiação , Células Ganglionares da Retina/efeitos da radiação , Opsinas de Bastonetes/metabolismo , Inconsciente Psicológico , Percepção Visual/efeitos da radiação , Ácido gama-Aminobutírico/metabolismo
17.
Neural Dev ; 14(1): 8, 2019 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470901

RESUMO

BACKGROUND: Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) respond directly to light and have been shown to mediate a broad variety of visual behaviors in adult animals. ipRGCs are also the first light sensitive cells in the developing retina, and have been implicated in a number of retinal developmental processes such as pruning of retinal vasculature and refinement of retinofugal projections. However, little is currently known about the properties of the six ipRGC subtypes during development, and how these cells act to influence retinal development. We therefore sought to characterize the structure, physiology, and birthdate of the most abundant ipRGC subtypes, M1, M2, and M4, at discrete postnatal developmental timepoints. METHODS: We utilized whole cell patch clamp to measure the electrophysiological and morphological properties of ipRGC subtypes through postnatal development. We also used EdU labeling to determine the embryonic timepoints at which ipRGC subtypes terminally differentiate. RESULTS: Our data show that ipRGC subtypes are distinguishable from each other early in postnatal development. Additionally, we find that while ipRGC subtypes terminally differentiate at similar embryonic stages, the subtypes reach adult-like morphology and physiology at different developmental timepoints. CONCLUSIONS: This work provides a broad assessment of ipRGC morphological and physiological properties during the postnatal stages at which they are most influential in modulating retinal development, and lays the groundwork for further understanding of the specific role of each ipRGC subtype in influencing retinal and visual system development.


Assuntos
Fenômenos Eletrofisiológicos/fisiologia , Retina/citologia , Retina/crescimento & desenvolvimento , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/metabolismo , Animais , Diferenciação Celular/fisiologia , Camundongos , Camundongos Transgênicos , Técnicas de Patch-Clamp , Células Ganglionares da Retina/classificação
18.
Cell Rep ; 29(11): 3349-3355.e2, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31825819

RESUMO

Light influences various behaviors and physiological processes that occur outside of our conscious perception, including circadian photoentrainment, sleep, and even learning and mood. The M1, melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) relay a combination of rod/cone and melanopsin signals to drive these functions. However, little is known about how M1 ipRGCs integrate these signals in low light. We measure the dim light response of M1 ipRGCs and find that they exhibit a wide spectrum of responses to dim, scotopic light stimulation that are driven by a combination of rod pathway input and melanopsin phototransduction. The presence of rod input to M1 ipRGCs correlates with larger and more complex dendritic arbors. Collectively, these results show variability in the rod input to M1 ipRGCs and a surprising contribution of melanopsin to the light responses of M1 ipRGCs at very low light.


Assuntos
Células Fotorreceptoras Retinianas Cones/metabolismo , Células Ganglionares da Retina/fisiologia , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Opsinas de Bastonetes/metabolismo , Visão Ocular , Animais , Dendritos/fisiologia , Feminino , Masculino , Camundongos , Estimulação Luminosa , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Ganglionares da Retina/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/fisiologia
19.
Elife ; 82019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31333190

RESUMO

The light environment greatly impacts human alertness, mood, and cognition by both acute regulation of physiology and indirect alignment of circadian rhythms. These processes require the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), but the relevant downstream brain areas involved remain elusive. ipRGCs project widely in the brain, including to the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Here we show that body temperature and sleep responses to acute light exposure are absent after genetic ablation of all ipRGCs except a subpopulation that projects to the SCN. Furthermore, by chemogenetic activation of the ipRGCs that avoid the SCN, we show that these cells are sufficient for acute changes in body temperature. Our results challenge the idea that the SCN is a major relay for the acute effects of light on non-image forming behaviors and identify the sensory cells that initiate light's profound effects on body temperature and sleep.


Assuntos
Ritmo Circadiano/genética , Células Ganglionares da Retina/metabolismo , Opsinas de Bastonetes/genética , Núcleo Supraquiasmático/metabolismo , Animais , Temperatura Corporal/genética , Encéfalo/metabolismo , Encéfalo/fisiologia , Humanos , Camundongos , Células Fotorreceptoras/metabolismo , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/metabolismo , Sono/genética , Sono/fisiologia , Vias Visuais/metabolismo
20.
Neuron ; 103(4): 642-657.e7, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31255486

RESUMO

Neuronal subtypes show diverse injury responses, but the molecular underpinnings remain elusive. Using transgenic mice that allow reliable visualization of axonal fate, we demonstrate that intrinsically photosensitive retinal ganglion cells (ipRGCs) are both resilient to cell death and highly regenerative. Using RNA sequencing (RNA-seq), we show genes that are differentially expressed in ipRGCs and that associate with their survival and axon regeneration. Strikingly, thrombospondin-1 (Thbs1) ranked as the most differentially expressed gene, along with the well-documented injury-response genes Atf3 and Jun. THBS1 knockdown in RGCs eliminated axon regeneration. Conversely, RGC overexpression of THBS1 enhanced regeneration in both ipRGCs and non-ipRGCs, an effect that was dependent on syndecan-1, a known THBS1-binding protein. All structural domains of the THBS1 were not equally effective; the trimerization and C-terminal domains promoted regeneration, while the THBS type-1 repeats were dispensable. Our results identify cell-type-specific induction of Thbs1 as a novel gene conferring high regenerative capacity.


Assuntos
Regeneração Nervosa/fisiologia , Células Ganglionares da Retina/fisiologia , Trombospondina 1/fisiologia , Animais , Apoptose , Axônios/metabolismo , Linhagem Celular , Feminino , Perfilação da Expressão Gênica , Genes Reporter , Fator de Crescimento Insulin-Like I/deficiência , Fator de Crescimento Insulin-Like I/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Compressão Nervosa , Traumatismos do Nervo Óptico/genética , Traumatismos do Nervo Óptico/fisiopatologia , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Opsinas de Bastonetes/deficiência , Opsinas de Bastonetes/fisiologia , Proteínas com Domínio T/deficiência , Proteínas com Domínio T/fisiologia , Trombospondina 1/biossíntese , Trombospondina 1/genética , Transcrição Gênica
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