Modulation of horizontal cell coupling in the vertebrate retina

The retina is a thin sheet of nerve cells at the back of the eye that converts the light of the visual world into a signal interpretable by the brain. Photoreceptors are the light-sensitive nerve cells of the retina and make connections (synapses) with bipolar cells and horizontal cells (HCs). Bipolar cells make synapses with amacrine cells and ganglion cells, the latter giving rise to processes (axons) that project to the brain as the optic nerve. At the level of the first synapse of the visual system, HCs enhance visual acuity by emphasizing differences in the visual scene. This is economical: the absolute intensity need not be encoded for every point in visual space, only the difference between a point in visual space (called the centre) and the background (called the surround).

HCs are thought to contribute to the surround. They are well suited for this being connected to each other by structures called gap junctions that allow electrical coupling. This means that HCs do not act as individual elements but as a sheet of coupled cells. The input they receive from photoreceptors is thus averaged, producing a measure of the background. The coupling of HCs is not static but can be modulated by the level of ambient illumination, suggesting that altering the size and strength of the surround is optimized as a function of ambient illumination level. Several neurochemical modulators, including dopamine, retinoic acid and nitric oxide, have been shown to reduce HC coupling, but when they act endogenously remains uncertain.

This research program seeks to understand the modulation of HC coupling in the vertebrate retina using a well-characterized model system, the goldfish. The role of neurochemical modulators, as mediators of the changes of HC coupling produced by altered ambient illumination, will be investigated by recording the light-evoked responses of HCs to determine their receptive-field size (a function of coupling) and by injecting tracers that pass through gap junctions (to assess directly the extent of coupling). Although there are neurons in the retina that could be the source of each neuromodulator, it is also possible that one (dopamine) is, in addition, provided by a non-neuronal source, the retinal pigmented epithelium (RPE). Using a readout of dopamine release in the retina that is easy to measure, light-dependent cone contraction, experiments are proposed to test the hypothesis that the RPE is a source of dopamine that could affect the neural retina.

This research program will add to our knowledge of the function of HCs in the vertebrate retina. Although curiosity-driven, basic research, such detailed knowledge of retinal function could ultimately prove useful for the development of retinal prosthesis or to guide machine vision design. The research program also provides several opportunities for undergraduate and graduate training.