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D.-Q. Zhang, K. Y. Wong, D. M. Berson, P. J. Sollars, D. G. McMahon, G. E. Pickard; Sustained Dopaminergic Amacrine Cells: Evidence for Inputs From Melanopsin Ganglion-Cell Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1517.
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Dopaminergic amacrine (DA) cells exhibit two classes of light responses: the majority are ON-Transient (TDA) cells driven by ON bipolar cells, whereas a minority are ON-Sustained (SDA) cells driven by an unidentified L-AP4-resistant source (Zhang et al., 2007). DA cells make contact with melanopsin ganglion cell (mel GC) processes. We sought to determine if SDA cells receive input from these inner retinal photoreceptors.
Experiments were performed with wild-type and rd/rd TH::RFP transgenic mice. DA cells were identified by fluorescence microscopy in the isolated retina, and recorded using whole-cell and loose patch voltage-clamp techniques. ICC was used to examine light-induced activation of c-fos.
Recordings from SDA cells in wild-type mouse retinas in the presence of L-AP4, a blocker of ON bipolar cell input, revealed long-latency light responses with sustained post-stimulus responses and a spectral sensitivity lambda-max of 478 ± 1.0 nm (n = 4), consistent with a melanopsin-based mechanism. In rd/rd mouse retinas, in which all rods and the great majority of cones had degenerated, SDA responses were preserved, but TDA responses were missing. 16/24 TH::RFP cells responded to light, and L-AP4 failed to block in 12/12 cells tested. The light responses of SDA cells in the presence of L-AP4, were long latency (463 ± 34 ms, log I = -2.55; n=7, mean ± S.E), persisted during the light pulse with a 3-fold increase in firing rate (5.1 ± 1.3 Hz baseline vs. 16.9 ± 1.9 Hz light, P<0.001), and continued for up to 15 seconds after light-offset. Light-induced expression of Fos was examined in wild-type (B6) and rd/rd mice killed 3 h after lights on or at the same time but in the dark. Light-induced the expression of Fos in TH cells in B6 and rd/rd mice (B6, n=3: light vs dark - 89.5% vs 0%; rd/rd, n=3: light vs dark - 21.4% vs 1.8% of TH cells were Fos positive). Light also induced Fos expression in mel GCs (B6, light vs dark -71.9% vs 0%; rd/rd light vs dark - 75.0% vs 0.8% of mel GCs were Fos positive).
Our results demonstrate that a subpopulation of DA cells respond to light stimulation independent of rod and cone photoreceptors with temporal and spectral characteristics consistent with input from melGC. This strongly suggests that melanopsin ganglion cells provide a centrifugal pathway within the retina through activation of SDA cells to regulate retinal visual processing and entrain the circadian clock.
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