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M. J. Van Hook, D. M. Berson; Dopaminergic Modulation of ipRGC Photoreception. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5030.
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Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and drive non-image-forming responses to light. Dopaminergic amacrine cells may modulate ipRGCs as dendrites of these two cell types make close contacts (Vugler et al., 2007) and dopamine may affect melanopsin expression (Sakamoto et al., 2005). Here, we asked whether dopamine acts directly on ipRGCs to modulate their photocurrent.
We selectively labeled rat ipRGCs by retrograde transport from the suprachiasmatic nucleus. After papain dissociation, labeled ganglion cells were either voltage clamped (whole-cell or perforated patch) or harvested for single-cell RT-PCR. Drugs were bath-applied or included in the recording pipette. Single-cell RT-PCR was used to confirm melanopsin expression and to examine the expression of dopamine receptor subtypes.
In nearly all ipRGCs, dopamine (10-1000 µM) attenuated the photocurrent (11 of 13 cells; 7.8-36% reduction). This effect was mimicked by a selective agonist of D1-family dopamine receptors (SKF38393; 1-200 µM; 2.8-83% reduction in photocurrent in 22 of 23 cells) but not by a selective D2-family agonist (quinpirole; 10-100 µM; no significant effect). The D1 agonist did not cause a change in input resistance (n=7). D1 receptors typically exert their effects by stimulation of adenylate cyclase (AC), elevation of cyclic AMP and activation of protein kinase A (PKA). This is probably how dopamine modulates ipRGC photocurrent, because co-application of an AC activator (forskolin; 20 µM) and a phosphodiesterase inhibitor (IBMX; 100 µM) also attenuated the photocurrent (n=6, 49-95% reduction). Also, the effects of activating D1 receptors (by SKF38393) on the photocurrent were blocked by intracellular infusion of a PKA inhibitor (KT5720; 1 µM; n=6). By single-cell RT-PCR, we detected D1 receptor expression in 71% (n=14) of melanopsin-expressing cells and D5 receptor expression in only 12% (n=26).
Dopamine, a key retinal circadian and adaptional modulator, attenuates the intrinsic photocurrent of ipRGCs. It does so through activation of D1-subtype dopamine receptors and a cAMP/PKA-dependent pathway. This signaling pathway may be a major contributor to circadian and/or light-adaptive modulation of ipRGCs and, thus, of non-image-forming visual networks.
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