Intraretinal signaling by ganglion cell photoreceptors to dopaminergic amacrine neurons

doi:10.1073/pnas.0803893105

Intraretinal signaling by ganglion cell photoreceptors to dopaminergic amacrine neurons

*Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235;
^‡Department of Neuroscience, Brown University, Providence, RI 02912; and
^§Department of Biomedical Sciences, Division of Neuroscience, Colorado State University, Fort Collins, CO 80523

Edited by John E. Dowling, Harvard University, Cambridge, MA, and approved July 14, 2008
↵^†D.-Q.Z. and K.Y.W. contributed equally to this work. (received for review April 22, 2008)

Abstract

Retinal dopaminergic amacrine neurons (DA neurons) play a central role in reconfiguring retinal function according to prevailing illumination conditions, yet the mechanisms by which light regulates their activity are poorly understood. We investigated the means by which sustained light responses are evoked in DA neurons. Sustained light responses were driven by cationic currents and persisted in vitro and in vivo in the presence of L-AP4, a blocker of retinal ON-bipolar cells. Several characteristics of these L-AP4-resistant light responses suggested that they were driven by melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), including long latencies, marked poststimulus persistence, and a peak spectral sensitivity of 478 nm. Furthermore, sustained DA neuron light responses, but not transient DA neuron responses, persisted in rod/cone degenerate retinas, in which ipRGCs account for virtually all remaining retinal phototransduction. Thus, ganglion-cell photoreceptors provide excitatory drive to DA neurons, most likely by way of the coramification of their dendrites and the processes of DA neurons in the inner plexiform layer. This unprecedented centrifugal outflow of ganglion-cell signals within the retina provides a novel basis for the restructuring of retinal circuits by light.

Footnotes

^‖To whom correspondence should be addressed at:
Department of Biological Sciences, Vanderbilt University, Vanderbilt University Station B, Box 35-1634, Nashville, TN 37235-1634.
E-mail: douglas.g.mcmahon{at}vanderbilt.edu
Author contributions: D.-Q.Z., K.Y.W., P.J.S., D.M.B., G.E.P., and D.G.M. designed research; D.-Q.Z., K.Y.W., P.J.S., G.E.P., and D.G.M. performed research; D.-Q.Z., K.Y.W., P.J.S., and G.E.P. analyzed data; and D.M.B. and D.G.M. wrote the paper.
↵^¶Present address: Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, NE 68583.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0803893105/DCSupplemental.