Heterogeneity of intrinsically photosensitive retinal ganglion cells in the mouse revealed by molecular phenotyping
Article first published online: 22 JAN 2013
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Comparative Neurology
Volume 521, Issue 4, pages 912–932, 1 March 2013
How to Cite
Karnas, D., Mordel, J., Bonnet, D., Pévet, P., Hicks, D. and Meissl, H. (2013), Heterogeneity of intrinsically photosensitive retinal ganglion cells in the mouse revealed by molecular phenotyping. J. Comp. Neurol., 521: 912–932. doi: 10.1002/cne.23210
- Issue published online: 22 JAN 2013
- Article first published online: 22 JAN 2013
- Accepted manuscript online: 8 AUG 2012 05:43AM EST
- Manuscript Accepted: 3 AUG 2012
- Manuscript Revised: 1 AUG 2012
- Manuscript Received: 16 NOV 2011
- Research was carried out within the scope of the Associated European Laboratory “European Laboratory for Circadian Research,” LEA CNRS-ULP-MPG (LEA No. 367) funded by the Max Planck Society, München, and CNRS, Paris and the CNRS-MPG neurosciences network (GDRE CNRS-MPG)
- microtubule associated protein-2 (MAP-2);
Intrinsically photosensitive retinal ganglion cell (ipRGC) types can be distinguished by their dendritic tree stratification and intensity of melanopsin staining. We identified heavily stained melanopsin-positive M1 cells branching in the outermost part of the inner plexiform layer (IPL) and weakly melanopsin-positive M2 cells branching in the innermost layer of the IPL. A third type can be distinguished by the displacement of the soma to the inner nuclear layer and has morphological similarities with either M1 cells or M2 cells, and is termed here displaced or M-d cells. The aim of the present study was to examine the phenotypic traits of ipRGC types. Using whole retinae from adult mice, we performed immunohistochemistry using melanopsin immunostaining and a number of antibodies directed against proteins typically expressed in retinal ganglion cells. The majority of M1 and M2 ipRGCs expressed Isl-1, microtubule associated protein-2 (MAP2), γ-synuclein, and NeuN, whereas Brn3 transcription factor and the different neurofilaments (NF68, NF160, NF200) were able to discriminate between ipRGC subtypes. Brn3 was expressed preferentially in M2 cells and in a small subpopulation of weakly melanopsin-positive M-d cells with similarities to M2 cells. All three neurofilaments were primarily expressed in large M2 cells with similarities to the recently described alpha-like M4 cells, but not in M1 cells. Expression of NF68 and NF160 was also observed in a few large M-d ipRGCs. These findings show that ipRGCs are not a phenotypically homogenous population and that specific neuronal markers (Brn3 and neurofilament) can partly distinguish between different ipRGC subtypes. J. Comp. Neurol. 521:912–932, 2013. © 2012 Wiley Periodicals, Inc.