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M.J. Gastinger, R.G. Yusupov, R.D. Glickman, D.W. Marshak; Histamine Modulates Spontaneous and Light Evoked Activity of Rat Ganglion Cells in vitro . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5175.
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Purpose: In mammals, centrifugal axons projecting from the hypothalamus to the retina use histamine as a neurotransmitter. To determine the function of this pathway, histamine receptors were localized and the effects of histamine on ganglion cells were studied in the rat retina. Methods: Extracellular recordings were made in vitro using a superfused flattened eyecup preparation. Histamine (0.5-50µM) as well as H3 agonists and antagonists were added to the superfusate. Histamine receptors were localized in frozen sections using antibodies against H3 (Chemicon). Results: Histamine modulated the light responses of sustained-ON and transient-ON ganglion cells decreasing the ON responses and increasing the OFF responses. In some cases, cells with no OFF response developed significant OFF responses when histamine was administered. In the 11 OFF cells in the sample, the light responses of only 2 were affected by histamine; both were inhibited slightly. In dark-adapted retinas, histamine increased the rate of spontaneous firing of both ON and OFF cells in a dose dependent manner, giving a half-maximal responses at 4µM. Histamine is less effective under steady photopic background light. In a low calcium (0.2mM), high magnesium (20mM) Ames medium, histamine (20µM) had no effect. At least some of the effects were mediated by H3. The H3 agonist, R-α-methylhistamine (5µM) also had excitatory effects. The H3 antagonist, thioperamide (10µM), diminished the effects of exogenous histamine. Punctate H3 immunoreactivity was localized in the outer plexiform layer. Conclusions: In rats, histaminergic neurons are most active in the night, and their major effect in the retina would be to increase the sensitivity to decrements in illumination.
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