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C. S. Cowan, M. M. Abd-El-Barr, F. R. Postma, D. E. Bramblett, J. Lem, D. L. Paul, S. M. Wu; Genetic Dissection of Rod and Cone Synaptic Inputs to ON/OFF and Transient/Sustained Light Responses of Retinal Ganglion Cells in the Mouse. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6152.
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© ARVO (1962-2015); The Authors (2016-present)
To understand the relative contributions of different rod and cone pathways to light ON versus OFF evoked responses of transient and sustained firing retinal ganglion cells (RGCs) in the mammalian retina.
A multi-electrode array (MEA) was used to record light responses from dark-adapted RGCs in wild type (C57/Bl6) mice, connexin36 (Cx36) KO mice, Bhlhb4 KO mice (which have no rod bipolar cells (DBCrs)), and rod transducina KO (Tra) mice. Flashed stimuli included a wide range of intensities, from 10^-2 Rh*/rod to 10^5 Rh*/rod. Spikes were sorted into neural units, and units were then categorized by response type.
(1) In wild type mice, we recorded from transient ON and OFF, sustained ON and OFF, and transient ON/OFF RGCs. We first found evidence of four major classes of ON responses, and are now extending the scheme to OFF responses. Type I, II, and III RGC responses operate in a narrow range at different sensitivities. Type I responses, the most sensitive, receive direct rod input while Type III responses, the least sensitive, had a range suggestive of cone input. Type II fell in between, matching the range of a previously observed ERG b-wave dip in Cx36 KO mice, and likely result from rod-cone coupling. Type IV responses had a wide dynamic range, spanning the operating ranges of the first three types. Preliminary results also suggest that the majority of these wide-range RGCs are of the sustained variety, perhaps acting as a measure of mean intensity. (2) In the Tra KO mice, we observed only Type III ON/OFF responses, consistent with an absence of all rod pathway responses. (3) In the Bhlhb4 KO mice we recorded Type III and Type IV responses, consistent with cone pathway preservation and the existence of DBCr independent rod pathways. (4) In the Cx36 KO mice, we recorded Type III and Type IV responses, suggesting a DBCr and rod-cone coupling independent rod pathway. (5) Analysis of the OFF pathway is ongoing, and will perhaps shed light on asymmetries of the ON and OFF retinal pathways in their dependence on rod and cone pathways.
By comparing three strains of mice with known retinal defects to wild type animals, we have genetically isolated four RGC response types with different rod and cone contributions. Current evidence suggests these response types are preserved among both ON and OFF, and transient/sustained firing RGCs.
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