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David W. Marshak, Alejandro Vila, Stephen Mills, Hideo Hoshi, Hiromasa Satoh, Peter R. MacLeish, Daniel Marshak, John O'Brien; Histamine Receptors of Cones and Horizontal Cells in Macaque Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4112.
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© ARVO (1962-2015); The Authors (2016-present)
In primates, the retina receives input from histaminergic neurons in the posterior hypothalamus that are active during the day. The goal of these experiments was to understand how this input contributes to information processing in the macaque retina by localizing histamine receptors (HR) and studying the effects of histamine on the neurons that express them.
Previously, HR3 was localized to the tips of ON bipolar cell dendrites, and histamine was found to hyperpolarize the cells via this receptor. To localize the other HR types, antisera were raised in goats against synthetic peptides corresponding to the second extracellular loop of HR1 and to an intracellular domain near the carboxyl terminus of HR2. Macaque retinal tissue was labeled with these antisera, primary antisera from other species and affinity-purified secondaty antibodies and then analyzed by confocal microscopy. HR mRNA was localized in macaque retina by in situ hybridization using digoxigenin-labeled RNA probes derived from human HR1 and HR2 cDNAs. The effect of histamine on the hyperpolarization-activated cation current (Ih) in primate cones was studied using patch electrodes in macaque retinal slices. .
The antibody to HR1 labeled both types of horizontal cells and a small number of unidentified amacrine cell perikarya. Horizontal cell perikarya expressed HR1 mRNA, but the strongest labeling was observed in their primary dendrites in the outer plexiform layer. The antiserum against HR2 is the first to ever label these receptors in the central nervous system. It labeled puncta closely associated, but not colocalized, with synaptic ribbons inside cone pedicles. Perikarya of cones expressed HR2 mRNA. 5 µM histamine reduced Ih at moderately hyperpolarized potentials, but not the maximal current. This shift in the activation voltage of Ih would counteract the effects of bright, ambient light, increasing the operating range of cones.
All three major targets of histamine in macaque retina are neurons ramifying in the outer plexiform layer, findings suggesting that histamine release during the day modulates transmission at photoreceptor synapses. Because the retinopetal axons containing histamine terminate in the inner plexiform layer, histamine acts primarily via volume transmission.
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