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1.
Nat Commun ; 10(1): 4017, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488831

RESUMO

An animal's motion through the environment can induce large and frequent fluctuations in light intensity on the retina. These fluctuations pose a major challenge to neural circuits tasked with encoding visual information, as they can cause cells to adapt and lose sensitivity. Here, we report that sensitization, a short-term plasticity mechanism, solves this difficult computational problem by maintaining neuronal sensitivity in the face of these fluctuations. The numerically dominant output pathway in the macaque monkey retina, the midget (parvocellular-projecting) pathway, undergoes sensitization under specific conditions, including simulated eye movements. Sensitization is present in the excitatory synaptic inputs from midget bipolar cells and is mediated by presynaptic disinhibition from a wide-field mechanism extending >0.5 mm along the retinal surface. Direct physiological recordings and a computational model indicate that sensitization in the midget pathway supports accurate sensory encoding and prevents a loss of responsiveness during dynamic visual processing.


Assuntos
Retina/fisiologia , Neurônios Retinianos/fisiologia , Vias Visuais/fisiologia , Animais , Percepção de Cores/fisiologia , Eletrofisiologia , Macaca , Macaca fascicularis , Macaca mulatta , Macaca nemestrina , Modelos Biológicos , Percepção de Movimento/fisiologia , Estimulação Luminosa , Primatas , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Ganglionares da Retina/fisiologia
2.
Horm Behav ; 114: 104539, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31199904

RESUMO

Visual communication is used widely across the animal kingdom to convey crucial information about an animals' identity, reproductive status, and sex. Although it is well-demonstrated that auditory and olfactory sensitivity can change with reproductive state, fewer studies have tested for plasticity in the visual system, a surprising detail since courtship and mate choice behaviors in many species are largely dependent on visual signals. Here, we tested for reproductive state-dependent plasticity in the eye of the cichlid fish Astatotilapia burtoni using behavioral, gene expression, neural activation, and electrophysiology techniques. Males court ovulated females more intensely than gravid females, and ovulated females were more responsive to male courtship behaviors than gravid females. Using electroretinography to measure visual sensitivity in dark-adapted fish, we revealed that gravid, reproductively-ready females have increased visual sensitivity at wavelengths associated with male courtship coloration compared to non-gravid females. After ovulation was hormonally induced, female's spectral sensitivity further increased compared to pre-injection measurements. This increased sensitivity after hormone injection was absent in non-gravid females and in males, suggesting an ovulation-triggered increase in visual sensitivity. Ovulated females had higher mRNA expression levels of reproductive neuromodulatory receptors (sex-steroids; gonadotropins) in the eye than nonovulated females, whereas males had similar expression levels independent of reproductive/social state. In addition, female mate choice-like behaviors positively correlated with expression of gonadotropin system receptors in the eye. Collectively, these data provide crucial evidence linking endocrine modulation of visual plasticity to mate choice behaviors in females.


Assuntos
Ciclídeos/fisiologia , Fenômenos Fisiológicos Oculares , Reprodução/fisiologia , África , Animais , Comportamento Animal/fisiologia , Eletrorretinografia/veterinária , Feminino , Hormônios Esteroides Gonadais/metabolismo , Masculino , Plasticidade Neuronal/fisiologia , Neurônios Retinianos/fisiologia , Olfato , Vias Visuais/fisiologia
3.
Exp Eye Res ; 182: 85-92, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30902621

RESUMO

Many neurodegenerations, including those of the visual system, have complex etiologies that include roles for both neurons and glia. In the retina there is evidence that retinal astrocytes play an important role in neurodegeneration. There are several approaches for isolating and growing primary retinal astrocytes, however, they often lead to different results. In this study, we examined the influence of culture conditions on phenotypic maturation of primary, purified retinal glia. We compared retinal astrocytes and Müller glia purified by immunomagnetic separation, as differentiation between these astrocyte subtypes is critical and immuno-based methods are the standard practice of purification. We found that while time in culture impacts the health and phenotype of both astrocytes and Müller glia, the phenotypic maturation of retinal astrocytes was most impacted by serum factors. These factors appeared to actively regulate intermediate filament phenotypes in a manner consistent with the induction of astrocyte-mesenchymal transition (AMT). This propensity for retinal astrocytes to shift along an AMT continuum should be considered when interpreting resulting data. Our goal is that this study will help standardize the field so that studies are replicable, comparable, and as accurate as possible for subsequent interpretation of findings.


Assuntos
Astrócitos/fisiologia , Diferenciação Celular , Neuroglia/fisiologia , Retina/citologia , Neurônios Retinianos/fisiologia , Animais , Comunicação Celular/fisiologia , Técnicas de Cultura de Células , Meios de Cultura/farmacologia , Fenótipo , Ratos , Ratos Sprague-Dawley
4.
Neuroscience ; 406: 140-149, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30826521

RESUMO

Diabetic retinopathy, a leading cause of vision loss, was considered as a solely vascular disorder but some recent studies suggest that retinal neurons may be affected much before the appearance of vascular lesions. However, the cellular processes involved in diabetes-induced degeneration of retinal neurons are poorly understood. Calcium (Ca2+) signaling plays a key role in normal functioning of neurons, and its dysregulation may lead to degeneration of neurons. Mitochondria are crucial components involved in the regulation of intracellular Ca2+ signaling. In this study, we have investigated the effects of diabetes on Ca2+ signaling in retinal neurons. The study was performed in rat retinal neurons cultured in high glucose condition (HGC) for 7-14 days and in acutely prepared retinal slices isolated from diabetic rats. When Ca2+ influx was induced by depolarization of neurons with 60 mM KCl in HGC neurons, the Ca2+ rise was sustained for a much longer duration as compared to controls, suggesting perturbation of Ca2+ buffering. In addition, HGC neurons also showed notably enhanced Ca2+ load in the mitochondria, which was accompanied by depolarization of mitochondrial membrane and enhanced reactive oxygen species formation. Similar results were obtained in acutely prepared retinal slices from control and diabetic rats. The depolarization of mitochondrial membrane was more pronounced in the neurons of the inner nuclear layer of diabetic rats. The physiological changes in mitochondria were observed as early as 9 weeks post diabetes induction. Thus, we report here that the intracellular Ca2+ signaling and mitochondrial function in retinal neurons are altered at an early stage of diabetes.


Assuntos
Sinalização do Cálcio/fisiologia , Diabetes Mellitus Experimental/metabolismo , Potencial da Membrana Mitocondrial/fisiologia , Mitocôndrias/fisiologia , Neurônios Retinianos/fisiologia , Animais , Células Cultivadas , Diabetes Mellitus Experimental/patologia , Masculino , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
5.
Med Sci Monit ; 25: 1001-1008, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30720005

RESUMO

BACKGROUND The aim of this study was to assess and compare peripapillary retinal nerve fiber layer (RNFL) thickness in patients with Alzheimer's disease (AD), primary open-angle glaucoma (POAG), preperimetric glaucoma (PPG), and healthy controls with the use of Spectral Domain Optical Coherence Tomography (SD-OCT). MATERIAL AND METHODS Thirty patients with AD, 30 patients with POAG, 30 patients with PPG, and 30 healthy controls were enrolled in this cross-sectional study. Only 1 randomly selected eye of each patient was analyzed. Every subject underwent a thorough ophthalmological examination and OCT of the optic disc. The peripapillary RNFL thickness in each of the 6 sectors and globally was analyzed. RESULTS The RNFL was thinnest in patients with POAG. The mean RNFL thickness value was 60.97±12.97 µm and it was significantly lower than in healthy controls (106.30±8.95 µm), patients with PPG (93.20±12.04 µm), and AD patients (95.73±13.52 µm). Mean RNFL thickness in patients with AD was significantly lower when compared to healthy controls, and was higher compared to eyes with POAG, while there were no significant differences compared to patients with PPG. CONCLUSIONS Neuronal damage in the central nervous system (CNS) also affects to retinal axons. A major problem is to distinguish the cause for a moderate decrease in the RNFL thickness. This is particularly true for patients with glaucoma who have not been diagnosed with changes in the visual field. It is not possible to distinguish the cause of a mild decrease in the RNFL thickness based on the SD-OCT. This may result in misdiagnosis of glaucoma, unnecessary use of anti-glaucoma eye drops, and a delayed diagnosis of AD.


Assuntos
Neurônios Retinianos/citologia , Neurônios Retinianos/fisiologia , Tomografia de Coerência Óptica/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Estudos de Casos e Controles , Estudos Transversais , Feminino , Glaucoma/complicações , Glaucoma/diagnóstico , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/diagnóstico , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Fibras Nervosas/fisiologia , Curva ROC , Retina , Células Ganglionares da Retina , Campos Visuais
6.
Biol Aujourdhui ; 212(1-2): 1-11, 2018.
Artigo em Francês | MEDLINE | ID: mdl-30362450

RESUMO

Dry eye disease (DED) is a common chronic condition with multifactorial etiologies that is increasing in prevalence worldwide, up to 20% in the elderly. The economic burden and impact of DED on vision, quality of life, work productivity, psychological and physical impact of pain, are considerable. Chronic ocular pain is the most common symptom of DED and there is currently no topical ocular analgesic therapy available to treat this debilitating disease. Eye pain can be perceived as itch, irritation, dryness, grittiness, burning, aching, and light sensitivity. Ocular pain is triggered by corneal nociceptors (cornea being the most sensory innervated tissue of the body). It was clearly established that repeated direct damage to ocular surface and per se corneal nerves can cause peripheral and central sensitization mechanisms explaining the ocular pain in some patients with DED. However, the brain regions and the neuronal pathways associated with ocular pain are still unclear. Thus, a better characterization of chronic ocular pain and an understanding of the peripheral and central molecular and cellular mechanisms involved are crucial issues for developing effective management and therapeutic strategy to alleviate ocular pain. In this review, we first describe the nociceptive corneal nerve pathways and the classification and the neurochemistry of primary afferents innervating the cornea. Then, an update of the fundamental and clinical studies related to the inflammatory processes linked to ocular pain is detailed. The last part of the review presents the diagnostic tools used in clinic for evaluating corneal sensitivity and corneal inflammation.


Assuntos
Dor Crônica/etiologia , Dor Ocular/etiologia , Dor Crônica/patologia , Compreensão , Córnea/anatomia & histologia , Córnea/inervação , Córnea/patologia , Síndromes do Olho Seco/complicações , Síndromes do Olho Seco/patologia , Dor Ocular/patologia , Humanos , Neurônios Retinianos/citologia , Neurônios Retinianos/patologia , Neurônios Retinianos/fisiologia , Gânglio Trigeminal/citologia , Gânglio Trigeminal/patologia , Gânglio Trigeminal/fisiologia
7.
Neuron ; 99(6): 1145-1154.e6, 2018 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-30197236

RESUMO

Distinct neuronal types connect in complex ways to generate functional neural circuits. The molecular diversity required to specify this connectivity could be supplied by multigene families of synaptic recognition molecules, but most studies to date have assessed just one or a few members at a time. Here, we analyze roles of cadherins (Cdhs) in formation of retinal circuits comprising eight neuronal types that inform the brain about motion in four directions. We show that at least 15 classical Cdhs are expressed by neurons in these circuits and at least 6 (Cdh6-10 and 18) act individually or in combinations to promote specific connectivity among the cells. They act in part by directing the processes of output neurons and excitatory interneurons to a cellular scaffold formed by inhibitory interneurons. Because Cdhs are expressed combinatorially by many central neurons, similar interactions could be involved in patterning circuits throughout the brain.


Assuntos
Caderinas/metabolismo , Dendritos/fisiologia , Interneurônios/fisiologia , Neurônios Retinianos/fisiologia , Sinapses/fisiologia , Animais , Camundongos , Retina/fisiologia , Células Ganglionares da Retina/fisiologia
8.
Annu Rev Vis Sci ; 4: 165-192, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30095374

RESUMO

Visual motion on the retina activates a cohort of retinal ganglion cells (RGCs). This population activity encodes multiple streams of information extracted by parallel retinal circuits. Motion processing in the retina is best studied in the direction-selective circuit. The main focus of this review is the neural basis of direction selectivity, which has been investigated in unprecedented detail using state-of-the-art functional, connectomic, and modeling methods. Mechanisms underlying the encoding of other motion features by broader RGC populations are also discussed. Recent discoveries at both single-cell and population levels highlight the dynamic and stimulus-dependent engagement of multiple mechanisms that collectively implement robust motion detection under diverse visual conditions.


Assuntos
Mamíferos/fisiologia , Percepção de Movimento/fisiologia , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Neurônios Retinianos/fisiologia , Células Amácrinas/fisiologia , Animais , Inibição Neural/fisiologia , Sinapses/fisiologia , Vias Visuais/fisiologia
9.
Cell ; 174(3): 607-621.e18, 2018 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-30033367

RESUMO

Many animals rely on vision to detect, locate, and track moving objects. In Drosophila courtship, males primarily use visual cues to orient toward and follow females and to select the ipsilateral wing for courtship song. Here, we show that the LC10 visual projection neurons convey essential visual information during courtship. Males with LC10 neurons silenced are unable to orient toward or maintain proximity to the female and do not predominantly use the ipsilateral wing when singing. LC10 neurons preferentially respond to small moving objects using an antagonistic motion-based center-surround mechanism. Unilateral activation of LC10 neurons recapitulates the orienting and ipsilateral wing extension normally elicited by females, and the potency with which LC10 induces wing extension is enhanced in a state of courtship arousal controlled by male-specific P1 neurons. These data suggest that LC10 is a major pathway relaying visual input to the courtship circuits in the male brain.


Assuntos
Neurônios Retinianos/fisiologia , Comportamento Sexual Animal/fisiologia , Visão Ocular/fisiologia , Animais , Encéfalo , Corte , Sinais (Psicologia) , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/fisiologia , Feminino , Interneurônios/fisiologia , Masculino , Neurônios/fisiologia , Acuidade Visual/fisiologia , Córtex Visual/fisiologia
10.
Neural Netw ; 105: 197-205, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29870927

RESUMO

We propose a coupled convolution layer comprising multiple parallel convolutions with mutually constrained filters. Inspired by biological human vision mechanism, we constrain the convolution filters such that one set of filter weights should be geometrically rotated, mirrored, or be the negative of the other. Our analysis suggests that the coupled convolution layer is more effective for lower layer where feature maps preserve geometric properties. Experimental comparisons demonstrate that the proposed coupled convolution layer performs slightly better than the original layer while decreasing the number of parameters. We evaluate its effect compared to non-constrained convolution layer using the CIFAR-10, CIFAR-100, and PlanktonSet 1.0 datasets.


Assuntos
Aprendizado de Máquina , Neurônios Retinianos/fisiologia , Humanos , Modelos Neurológicos
11.
Annu Rev Vis Sci ; 4: 45-77, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29852094

RESUMO

Microglia, the primary resident immune cell type, constitute a key population of glia in the retina. Recent evidence indicates that microglia play significant functional roles in the retina at different life stages. During development, retinal microglia regulate neuronal survival by exerting trophic influences and influencing programmed cell death. During adulthood, ramified microglia in the plexiform layers interact closely with synapses to maintain synaptic structure and function that underlie the retina's electrophysiological response to light. Under pathological conditions, retinal microglia participate in potentiating neurodegeneration in diseases such as glaucoma, retinitis pigmentosa, and age-related neurodegeneration by producing proinflammatory neurotoxic cytokines and removing living neurons via phagocytosis. Modulation of pathogenic microglial activation states and effector mechanisms has been linked to neuroprotection in animal models of retinal diseases. These findings have led to the design of early proof-of-concept clinical trials with microglial modulation as a therapeutic strategy.


Assuntos
Microglia/fisiologia , Retina/embriologia , Retina/fisiologia , Doenças Retinianas/patologia , Animais , Humanos , Microglia/patologia , Terapia de Alvo Molecular/métodos , Doenças Retinianas/terapia , Neurônios Retinianos/fisiologia
12.
Annu Rev Vis Sci ; 4: 263-285, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29856937

RESUMO

The thalamocortical pathway is the main route of communication between the eye and the cerebral cortex. During embryonic development, thalamocortical afferents travel to L4 and are sorted by receptive field position, eye of origin, and contrast polarity (i.e., preference for light or dark stimuli). In primates and carnivores, this sorting involves numerous afferents, most of which sample a limited region of the binocular field. Devoting abundant thalamocortical resources to process a limited visual field has a clear advantage: It allows many stimulus combinations to be sampled at each spatial location. Moreover, the sampling efficiency can be further enhanced by organizing the afferents in a cortical grid for eye input and contrast polarity. We argue that thalamocortical interactions within this eye-polarity grid can be used to represent multiple stimulus combinations found in nature and to build an accurate cortical map for multidimensional stimulus space.


Assuntos
Vias Neurais/fisiologia , Neurônios Retinianos/fisiologia , Tálamo/fisiologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Mapeamento Encefálico , Olho/embriologia , Humanos , Vias Neurais/embriologia , Neurônios Aferentes/fisiologia , Tálamo/embriologia , Córtex Visual/embriologia , Campos Visuais/fisiologia , Vias Visuais/fisiologia
13.
J Neurophysiol ; 120(2): 854-866, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29766767

RESUMO

Circuit operations are determined jointly by the properties of the circuit elements and the properties of the connections among these elements. In the nervous system, neurons exhibit diverse morphologies and branching patterns, allowing rich compartmentalization within individual cells and complex synaptic interactions among groups of cells. In this review, we summarize work detailing how neuronal morphology impacts neural circuit function. In particular, we consider example neurons in the retina, cerebral cortex, and the stomatogastric ganglion of crustaceans. We also explore molecular coregulators of morphology and circuit function to begin bridging the gap between molecular and systems approaches. By identifying motifs in different systems, we move closer to understanding the structure-function relationships that are present in neural circuits.


Assuntos
Córtex Cerebral/citologia , Córtex Cerebral/fisiologia , Gânglios dos Invertebrados/citologia , Gânglios dos Invertebrados/fisiologia , Neurônios Retinianos/citologia , Neurônios Retinianos/fisiologia , Animais , Córtex Cerebral/crescimento & desenvolvimento , Crustáceos/citologia , Crustáceos/fisiologia , Dendritos , Gânglios dos Invertebrados/crescimento & desenvolvimento , Humanos , Vias Neurais/citologia , Vias Neurais/fisiologia , Neurônios/citologia , Neurônios/fisiologia , Estrigiformes/anatomia & histologia , Estrigiformes/fisiologia
14.
Adv Exp Med Biol ; 1074: 135-144, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29721937

RESUMO

Adaptive optics retinal imaging of fluorescent calcium indicators is a minimally invasive method used to study retinal physiology over extended periods of time. It has potential for discovering novel retinal circuits, tracking retinal function in animal models of retinal disease, and assessing vision restoration therapy. We previously demonstrated functional adaptive optics imaging of retinal neurons in the living eye using green fluorescent calcium indicators; however, the use of green fluorescent indicators presents challenges that stem from the fact that they are excited by short-wavelength light. Using red fluorescent calcium indicators such as jRGECO1a, which is excited with longer-wavelength light (~560 nm), makes imaging approximately five times safer than using short-wavelength light (~500 nm) used to excite green fluorescent calcium indicators such as GCaMP6s. Red fluorescent indicators also provide alternative wavelength imaging regimes to overcome cross talk with the sensitivities of intrinsic photoreceptors and blue light-activated channelrhodopsins. Here we evaluate jRGECO1a for in vivo functional adaptive optics imaging of retinal neurons using single-photon excitation in mice. We find that jRGECO1a provides similar fidelity as the established green indicator GCaMP6s.


Assuntos
Cálcio/análise , Proteínas de Fluorescência Verde/análise , Microscopia Intravital/métodos , Proteínas Luminescentes/análise , Imagem Molecular/métodos , Imagem Óptica/métodos , Óptica e Fotônica/métodos , Neurônios Retinianos/ultraestrutura , Animais , Dependovirus/genética , Feminino , Corantes Fluorescentes , Genes Reporter , Vetores Genéticos , Proteínas de Fluorescência Verde/genética , Proteínas Luminescentes/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios Retinianos/química , Neurônios Retinianos/fisiologia
15.
PLoS One ; 13(4): e0196365, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29702674

RESUMO

The ability to express a gene of interest in a spatio-temporal manner using Gal4-UAS system has allowed the use of Drosophila model to study various biological phenomenon. During Drosophila eye development, a synchronous wave of differentiation called Morphogenetic furrow (MF) initiates at the posterior margin resulting in differentiation of retinal neurons. This synchronous differentiation is also observed in the differentiating retina of vertebrates. Since MF is highly dynamic, it can serve as an excellent model to study patterning and differentiation. However, there are not any Gal4 drivers available to observe the gain- of- function or loss- of- function of a gene specifically along the dynamic MF. The decapentaplegic (dpp) gene encodes a secreted protein of the transforming growth factor-beta (TGF-beta) superfamily that expresses at the posterior margin and then moves with the MF. However, unlike the MF associated pattern of dpp gene expression, the targeted dpp-Gal4 driver expression is restricted to the posterior margin of the developing eye disc. We screened GMR lines harboring regulatory regions of dpp fused with Gal4 coding region to identify MF specific enhancer of dpp using a GFP reporter gene. We employed immuno-histochemical approaches to detect gene expression. The rationale was that GFP reporter expression will correspond to the dpp expression domain in the developing eye. We identified two new dpp-Gal4 lines, viz., GMR17E04-Gal4 and GMR18D08-Gal4 that carry sequences from first intron region of dpp gene. GMR17E04-Gal4 drives expression along the MF during development and later in the entire pupal retina whereas GMR18D08-Gal4 drives expression of GFP transgene in the entire developing eye disc, which later drives expression only in the ventral half of the pupal retina. Thus, GMR18D08-Gal4 will serve as a new reagent for targeting gene expression in the ventral half of the pupal retina. We compared misexpression phenotypes of Wg, a negative regulator of eye development, using GMR17E04-Gal4, GMR18D08-Gal4 with existing dpp-Gal4 driver. The eye phenotypes generated by using our newly identified MF specific driver are not similar to the ones generated by existing dpp-Gal4 driver. It suggests that misexpression studies along MF needs revisiting using the new Gal4 drivers generated in our studies.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/embriologia , Drosophila melanogaster/crescimento & desenvolvimento , Retina/embriologia , Retina/crescimento & desenvolvimento , Fatores de Transcrição/genética , Proteína Wnt1/genética , Animais , Animais Geneticamente Modificados , Padronização Corporal , Diferenciação Celular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Fluorescência Verde/metabolismo , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Nucleares/genética , Fenótipo , Proteínas Serina-Treonina Quinases/genética , Neurônios Retinianos/fisiologia , Transativadores/genética , Fator de Crescimento Transformador beta/metabolismo
16.
Elife ; 72018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29557782

RESUMO

In recent years, multielectrode arrays and large silicon probes have been developed to record simultaneously between hundreds and thousands of electrodes packed with a high density. However, they require novel methods to extract the spiking activity of large ensembles of neurons. Here, we developed a new toolbox to sort spikes from these large-scale extracellular data. To validate our method, we performed simultaneous extracellular and loose patch recordings in rodents to obtain 'ground truth' data, where the solution to this sorting problem is known for one cell. The performance of our algorithm was always close to the best expected performance, over a broad range of signal-to-noise ratios, in vitro and in vivo. The algorithm is entirely parallelized and has been successfully tested on recordings with up to 4225 electrodes. Our toolbox thus offers a generic solution to sort accurately spikes for up to thousands of electrodes.


Assuntos
Potenciais de Ação/fisiologia , Eletrodos , Eletrofisiologia/instrumentação , Neurônios Retinianos/fisiologia , Algoritmos , Animais , Simulação por Computador , Eletrofisiologia/métodos , Masculino , Camundongos , Modelos Neurológicos , Ratos Long-Evans , Processamento de Sinais Assistido por Computador
17.
Methods Mol Biol ; 1753: 3-25, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29564778

RESUMO

The mouse retina has a layered structure that is composed of five classes of neurons supported by Müller glial and pigment epithelial cells. Recent studies have made progress in the classification of bipolar and ganglion cells, and also in the wiring of rod-driven signaling, color coding, and directional selectivity. Molecular biological techniques, such as genetic manipulation, transcriptomics, and fluorescence imaging, have contributed a lot to these advancements. The mouse retina has consistently been an important experimental system for both basic and clinical neurosciences.


Assuntos
Rede Nervosa/citologia , Neurônios Retinianos/citologia , Epitélio Pigmentado da Retina/citologia , Animais , Genômica/métodos , Camundongos , Microscopia Eletrônica/métodos , Rede Nervosa/fisiologia , Rede Nervosa/ultraestrutura , Imagem Óptica/métodos , Neurônios Retinianos/fisiologia , Neurônios Retinianos/ultraestrutura , Epitélio Pigmentado da Retina/fisiologia , Epitélio Pigmentado da Retina/ultraestrutura , Transcriptoma/fisiologia
18.
J Diabetes Investig ; 9(5): 1041-1051, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29427460

RESUMO

AIMS/OBJECTIVE: The present study aimed to explore the effects of micro-ribonucleic acid-365 (miR-365) on apoptosis of retinal neurons by targeting insulin-like growth factor-1 (IGF-1) in diabetes mellitus rats. MATERIALS AND METHODS: High glucose-induced retinal neurons were assigned into the blank (with no plasmid transfection), negative control (with plasmid transfection), anti-miR-365 (transfected miR-365 antagomir), transfected IGF-1 short hairpin RNA plasmid (sh-IGF-1) and transfected miR-365 antagomir and IGF-1 shRNA plasmid (anti-miR-365 + sh-IGF-1) groups. Proliferation and apoptosis of retinal neurons were detected by 5-ethynyl-2'-deoxyuridine assay and Hoechst 33342 staining, respectively. Expressions of miR-365, IGF-1, Bcl-2-associated X protein (Bax) and Bcl-2 were determined by reverse transcription quantitative polymerase chain reaction and western blotting. A control group contained 10 healthy rats. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was used to evaluate apoptosis of retinal neurons in rats. RESULTS: In the anti-miR-365 group, the apoptosis rate and Bax expression were reduced in comparison with the negative control and blank groups, whereas the sh-IGF-1 and anti-miR-365 + sh-IGF-1 groups presented an opposite trend. Compared with the normal group, expressions of miR-365 and Bax were increased, and expressions of IGF-1 and Bcl-2 were decreased, with more apoptotic cells in diabetes mellitus rat models. The sh-IGF-1 group had lower Bax expression, and higher expressions of IGF-1 and Bcl-2 with fewer apoptotic cells. Additionally, Bax expression was upregulated, expressions of IGF-1 and Bcl-2 were downregulated, and apoptotic cells were higher in the anti-miR-365 + sh-IGF-1 groups than the anti-miR-365 group. CONCLUSION: The results of the present study suggest that suppressed miR-365 increases the IGF-1 expression, leading to anti-apoptotic effects on retinal neurons in diabetic rats.


Assuntos
Apoptose/fisiologia , Diabetes Mellitus Experimental/terapia , Marcação de Genes/métodos , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , MicroRNAs/antagonistas & inibidores , Neurônios Retinianos/fisiologia , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Relação Dose-Resposta a Droga , Fator de Crescimento Insulin-Like I/biossíntese , Fator de Crescimento Insulin-Like I/genética , Masculino , MicroRNAs/biossíntese , MicroRNAs/genética , RNA Interferente Pequeno/administração & dosagem , Ratos , Ratos Sprague-Dawley , Neurônios Retinianos/efeitos dos fármacos
19.
Trends Neurosci ; 41(4): 224-237, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29454561

RESUMO

The ability of the retina to adapt to changes in mean light intensity and contrast is well known. Classically, however, adaptation is thought to affect gain but not to change the visual modality encoded by a given type of retinal neuron. Recent findings reveal unexpected dynamic properties in mouse retinal neurons that challenge this view. Specifically, certain cell types change the visual modality they encode with variations in ambient illumination or following repetitive visual stimulation. These discoveries demonstrate that computations performed by retinal circuits with defined architecture can change with visual input. Moreover, they pose a major challenge for central circuits that must decode properties of the dynamic visual signal from retinal outputs.


Assuntos
Biologia Computacional , Retina/fisiologia , Neurônios Retinianos/fisiologia , Vias Visuais/fisiologia , Animais , Humanos , Células Ganglionares da Retina/fisiologia , Visão Ocular/fisiologia
20.
J Neurosci ; 38(11): 2713-2729, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29439167

RESUMO

The clustered protocadherins (Pcdhs) comprise 58 cadherin-related proteins encoded by three tandemly arrayed gene clusters, Pcdh-α, Pcdh-ß, and Pcdh-γ (Pcdha, Pcdhb, and Pcdhg, respectively). Pcdh isoforms from different clusters are combinatorially expressed in neurons. They form multimers that interact homophilically and mediate a variety of developmental processes, including neuronal survival, synaptic maintenance, axonal tiling, and dendritic self-avoidance. Most studies have analyzed clusters individually. Here, we assessed functional interactions between Pcdha and Pcdhg clusters. To circumvent neonatal lethality associated with deletion of Pcdhgs, we used Crispr-Cas9 genome editing in mice to combine a constitutive Pcdha mutant allele with a conditional Pcdhg allele. We analyzed roles of Pcdhas and Pcdhgs in the retina and cerebellum from mice (both sexes) lacking one or both clusters. In retina, Pcdhgs are essential for survival of inner retinal neurons and dendritic self-avoidance of starburst amacrine cells, whereas Pcdhas are dispensable for both processes. Deletion of both Pcdha and Pcdhg clusters led to far more dramatic defects in survival and self-avoidance than Pcdhg deletion alone. Comparisons of an allelic series of mutants support the conclusion that Pcdhas and Pcdhgs function together in a dose-dependent and cell-type-specific manner to provide a critical threshold of Pcdh activity. In the cerebellum, Pcdhas and Pcdhgs also cooperate to mediate self-avoidance of Purkinje cell dendrites, with modest but significant defects in either single mutant and dramatic defects in the double mutant. Together, our results demonstrate complex patterns of redundancy between Pcdh clusters and the importance of Pcdh cluster diversity in postnatal CNS development.SIGNIFICANCE STATEMENT The formation of neural circuits requires diversification and combinatorial actions of cell surface proteins. Prominent among them are the clustered protocadherins (Pcdhs), a family of ∼60 neuronal recognition molecules. Pcdhs are encoded by three closely linked gene clusters called Pcdh-α, Pcdh-ß, and Pcdh-γ. The Pcdhs mediate a variety of developmental processes, including neuronal survival, synaptic maintenance, and spatial patterning of axons and dendrites. Most studies to date have been limited to single clusters. Here, we used genome editing to assess interactions between Pcdh-α and Pcdh-γ gene clusters. We examined two regions of the CNS, the retina and cerebellum and show that the 14 α-Pcdhs and 22 γ-Pcdhs act synergistically to mediate neuronal survival and dendrite patterning.


Assuntos
Caderinas/genética , Sobrevivência Celular/genética , Dendritos/fisiologia , Neurônios Retinianos/fisiologia , Células Amácrinas/fisiologia , Animais , Axônios/fisiologia , Cerebelo/metabolismo , Feminino , Deleção de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação/fisiologia , Neurogênese , Células de Purkinje/fisiologia , Retina/crescimento & desenvolvimento , Retina/metabolismo , Sinapses/fisiologia
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