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NITRIC OXIDE NEUROMODULATION OF VERTEBRATE GAP JUNCTION-COUPLED RETINAL HORIZONTAL CELLS

Date

2022-08-18

Authors

Yousef, Tareq

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Abstract

Horizontal cells (HCs) are second-order neurons of the vertebrate retina that are thought to contribute to the generation of the surround component of center-surround receptive fields of bipolar and ganglion cells that are important for contrast detection. In goldfish retina, cone-driven HC somata (HCS) have axons that terminate as large axon terminals (HATs). Both HCS and HATs are gap junction (GJ)-coupled (by GJ proteins Cx53.8, Cx55.5, and possibly others), producing large receptive-fields. HCS coupling is modulated by ambient illumination and neuromodulators, such as nitric oxide (NO) and dopamine (DA), but few studies have examined HAT coupling. “Stab loading” of the GJ-permeable tracer Neurobiotin allowed for assessment of HAT GJ-coupling in the goldfish retina. A primary aim was to determine if NO and protein kinase G (PKG) are involved in the reduction of HC GJ coupling following exposure to bright light (light-adaptation). Light-adaptation reduced HAT GJ coupling, an effect that was mimicked by NO donor and a membrane permeable cyclic GMP analogue. The effect of light-adaptation was reduced by NO synthase and PKG inhibitors. PKG inhibitor also reduced the effect of light-adaptation on goldfish HCS receptive-field size (assessed by intracellular recording) and tracer coupling (applied by “cut-loading”) of mouse HCS. These results suggest that both HCS and HAT GJ coupling is reduced by light-adaptation and that this involves a NO/cyclic GMP/PKG pathway. A protein kinase A (PKA)>PKG inhibitor also reduced the effect of light-adaptation, possibly indicating PKG-PKA cross talk, a mechanism that has been proposed for the modulation of the GJ protein Cx35. The PKA>PKG inhibitor (but not the PKG inhibitor) blocked the effect of flickering light on HAT GJ coupling, consistent with previous studies of HCS that indicated that the effect of flickering light is mediated by DA acting via D1 DA receptors. Changes in HCS gap junction coupling by the level of ambient illumination could alter the size of the bipolar and ganglion cell surround. Although the function of HATs is uncertain, synaptic contacts with bipolar cells may indicate an alternate pathway for surround generation that could be modulated by the extent of HAT GJ coupling.

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Keywords

retina, nitric oxide, goldfish, neuromodulation, horizontal cell

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