Modulation of gap junction coupling in the vertebrate retina

The vertebrate retina is a thin sheet of central nervous system tissue lining the back of the eye that transduces the image of the visual world into an electrochemical signal and processes this signal generating parallel pathways encoding different aspect of the visual scene. Gap junctions, the structural correlate of direct electrical coupling between cells, are important participants in the circuitry of the vertebrate retina. The following research focuses on two different aspects of gap junction coupling in the vertebrate retina. First, we propose to continue our studies of the modulation of retinal horizontal cell coupling in the teleost retina by focusing on a potential new source of the neuromodulator dopamine. Second, we will further our study of the coupling of a new type of ganglion cell, the intrinsically light-sensitive, melanopsin-containing ganglion cells, in the mammalian retina.Dopamine (DA) is the best-known neuromodulator of horizontal cell activity. Until recently, the only known source of endogenous dopamine in the teleost retina was interplexiform cells. A possible additional source of DA in the retina has recently been identified. This source is the retinal pigmented epithelium (RPE), where the DA precursor L-DOPA could be synthesized by tyrosinase as part of the synthetic pathway associated with the synthesis of the RPE pigment melanin. We intend to study this potential source of DA by examining two known DA- and light-dependent features of the teleost retina, the movement of cones and the coupling of horizontal cells. These studies will use a zebrafish mutant that lacks tyrosinase and goldfish treated with tyrosinase inhibitors and will employ both anatomical and electrophysiological techniques.Previous work suggests that the intrinsic photosensitive retinal ganglion cells (ipRGCs) are gap junction coupled. We have published anatomical evidence that ipRGCs are coupled to a specific class of amacrine cells in the retina. We intend to determine if this coupling can be demonstrated physiologically, using calcium imaging, and will attempt to identify the type of gap junction that ipRGCs express.