Assuntos
Ritmo Circadiano/fisiologia , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/genética , Sequência de Aminoácidos , Animais , Expressão Gênica , Humanos , Camundongos , Células Fotorreceptoras de Vertebrados/fisiologia , Isoformas de Proteínas , Ratos , Opsinas de Bastonetes/química , Especificidade da EspécieRESUMO
Non-image related responses to light, such as the synchronization of circadian rhythms to the day/night cycle, are mediated by classical rod/cone photoreceptors and by a small subset of retinal ganglion cells that are intrinsically photosensitive, expressing the photopigment, melanopsin. This raises the possibility that the melanopsin cells may be serving as a conduit for photic information detected by the rods and/or cones. To test this idea, we developed a specific immunotoxin consisting of an anti-melanopsin antibody conjugated to the ribosome-inactivating protein, saporin. Intravitreal injection of this immunotoxin results in targeted destruction of melanopsin cells. We find that the specific loss of these cells in the adult mouse retina alters the effects of light on circadian rhythms. In particular, the photosensitivity of the circadian system is significantly attenuated. A subset of animals becomes non-responsive to the light/dark cycle, a characteristic previously observed in mice lacking rods, cones, and functional melanopsin cells. Mice lacking melanopsin cells are also unable to show light induced negative masking, a phenomenon known to be mediated by such cells, but both visual cliff and light/dark preference responses are normal. These data suggest that cells containing melanopsin do indeed function as a conduit for rod and/or cone information for certain non-image forming visual responses. Furthermore, we have developed a technique to specifically ablate melanopsin cells in the fully developed adult retina. This approach can be applied to any species subject to the existence of appropriate anti-melanopsin antibodies.
Assuntos
Ritmo Circadiano , Retina/efeitos dos fármacos , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Proteínas Inativadoras de Ribossomos Tipo 1/química , Animais , Comportamento Animal , Relógios Biológicos/efeitos dos fármacos , Relógios Biológicos/efeitos da radiação , Luz , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Fotoquímica/métodos , Retina/patologia , Retina/efeitos da radiação , Células Ganglionares da Retina/efeitos da radiação , Proteínas Inativadoras de Ribossomos Tipo 1/metabolismo , Opsinas de Bastonetes/química , Saporinas , Fatores de TempoRESUMO
The bed nucleus of the stria terminalis (BNST) is a basal forebrain structure involved in many motivational processes closely linked to stress regulation. The present study investigated the effect of bilateral lesions of the BNST in male Wistar rats on behavioral despair and navigational learning in the Morris water maze both of which present stressful challenges. Compared to controls, BNST-lesioned animals displayed longer duration of immobility in the second of two forced swim tests used to assess behavioral despair but performed similarly in the water maze task. The present results indicate strongly that the BNST is involved in the modulation of behavioral despair. Experimentally induced depression by BNST lesions does not impair learning and memory in the water maze suggesting a possible dissociation between BNST-mediated depression and cognitive performance.