RESUMO
Using the photopigment melanopsin, intrinsically photosensitive retinal ganglion cells (ipRGCs) respond directly to light to drive circadian clock resetting and pupillary constriction. We now report that ipRGCs are more abundant and diverse than previously appreciated, project more widely within the brain, and can support spatial visual perception. A Cre-based melanopsin reporter mouse line revealed at least five subtypes of ipRGCs with distinct morphological and physiological characteristics. Collectively, these cells project beyond the known brain targets of ipRGCs to heavily innervate the superior colliculus and dorsal lateral geniculate nucleus, retinotopically organized nuclei mediating object localization and discrimination. Mice lacking classical rod-cone photoreception, and thus entirely dependent on melanopsin for light detection, were able to discriminate grating stimuli from equiluminant gray and had measurable visual acuity. Thus, nonclassical retinal photoreception occurs within diverse cell types and influences circuits and functions encompassing luminance as well as spatial information.
Assuntos
Células Fotorreceptoras/metabolismo , Retina/citologia , Células Ganglionares da Retina/metabolismo , Opsinas de Bastonetes/metabolismo , Visão Ocular/fisiologia , Fosfatase Alcalina/metabolismo , Animais , Ritmo Circadiano , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Enucleação Ocular/métodos , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Regulação da Expressão Gênica/genética , Proteínas de Fluorescência Verde/genética , Técnicas In Vitro , Luz , Transdução de Sinal Luminoso/fisiologia , Aprendizagem em Labirinto/fisiologia , Potenciais da Membrana/fisiologia , Potenciais da Membrana/efeitos da radiação , Camundongos , Camundongos Knockout , Vias Neurais/metabolismo , Nistagmo Optocinético/genética , Técnicas de Patch-Clamp/métodos , Opsinas de Bastonetes/deficiência , Percepção Espacial/fisiologia , Transducina/genética , Transducina/metabolismo , Acuidade Visual/genética , Córtex Visual/metabolismoRESUMO
A key principle of retinal organization is that distinct ON and OFF channels are relayed by separate populations of bipolar cells to different sublaminae of the inner plexiform layer (IPL). ON bipolar cell axons have been thought to synapse exclusively in the inner IPL (the ON sublamina) onto dendrites of ON-type amacrine and ganglion cells. However, M1 melanopsin-expressing ganglion cells and dopaminergic amacrine (DA) cells apparently violate this dogma. Both are driven by ON bipolar cells, but their dendrites stratify in the outermost IPL, within the OFF sublamina. Here, in the mouse retina, we show that some ON cone bipolar cells make ribbon synapses in the outermost OFF sublayer, where they costratify with and contact the dendrites of M1 and DA cells. Whole-cell recording and dye filling in retinal slices indicate that type 6 ON cone bipolars provide some of this ectopic ON channel input. Imaging studies in dissociated bipolar cells show that these ectopic ribbon synapses are capable of vesicular release. There is thus an accessory ON sublayer in the outer IPL.
Assuntos
Células Amácrinas/fisiologia , Dopamina/metabolismo , Retina/citologia , Células Bipolares da Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/metabolismo , Sinapses/fisiologia , Animais , Estimulação Elétrica/métodos , Proteínas de Fluorescência Verde/genética , Técnicas In Vitro , Transdução de Sinal Luminoso/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Técnicas de Patch-Clamp , Estimulação Luminosa/métodos , Compostos de Piridínio/metabolismo , Compostos de Amônio Quaternário/metabolismo , Receptores de Glutamato Metabotrópico/genética , Opsinas de Bastonetes/genética , Sinapses/classificação , Potenciais Sinápticos/genética , Tirosina 3-Mono-Oxigenase/genética , Vias Visuais/fisiologia , beta-Galactosidase/genéticaRESUMO
The mammalian retina contains approximately 30 different morphological types of amacrine cells, receiving glutamatergic input from bipolar cells. In this study, we combined electrophysiological and pharmacological techniques in order to study the glutamate receptors expressed by different types of amacrine cells. Whole-cell currents were recorded from amacrine cells in vertical slices of the mouse retina. During the recordings the cells were filled with Lucifer Yellow/Neurobiotin allowing classification as wide-field or narrow-field amacrine cells. Amacrine cell recordings were also carried out in a transgenic mouse line whose glycinergic amacrine cells express enhanced green fluorescent protein (EGFP). Agonist-induced currents were elicited by exogenous application of NMDA, AMPA, and kainate (KA) while holding cells at -75 mV. Using a variety of specific agonists and antagonists (NBQX, AP5, cyclothiazide, GYKI 52466, GYKI 53655, SYM 2081) responses mediated by AMPA, KA, and NMDA receptors could be dissected. All cells (n = 300) showed prominent responses to non-NMDA agonists. Some cells expressed AMPA receptors exclusively and some cells expressed KA receptors exclusively. In the majority of cells both receptor types could be identified. NMDA receptors were observed in about 75% of the wide-field amacrine cells and in less than half of the narrow-field amacrine cells. Our results confirm that different amacrine cell types express distinct sets of ionotropic glutamate receptors, which may be critical in conferring their unique temporal responses to this diverse neuronal class.