Abstract
Purpose: :
Waves of correlated neural activity sweep across the early postnatal retina and contribute to the segregation and refinement of retinofugal projections. We have previously demonstrated that light alters this global, inner-retinal process by exciting melanopsin ganglion cells. Here we tested the hypothesis that photic modulation of retinal waves alters circuit maturation of retinofugal pathways.
Methods: :
At birth, we placed melanopsin knockout mice and wild-type littermate controls in continuous light. At postnatal day 7 (P7), we injected green fluorescent anterograde tracer into the left eye (cholera toxin B [CTB]-Alexa-488) and red tracer in the right (CTB-Alexa-594). At P8, the brains were fixed and sectioned (50µm). Images of the left and right dLGN in four sections from each mouse were captured using identical settings for the two tracers. For each pixel in the dLGN we calculated the log of the ratio of red and green channel intensities (Torborg and Feller 2004). We defined ‘unsegregated’ pixels as those with red and green signals that were more balanced than 99% of pixels within the most monocular sectors of the dLGN. We remained blind to genotype until all data was collected, processed and analyzed.
Results: :
In melanopsin knockout mouse pups reared in continuous light (P0-P8), the percentage of all dLGN pixels that were ‘unsegregated’ was significantly higher than in wild-type littermate controls (P<0.05; n=2 knockout mice and 4 wild-type mice; 8 sections/mouse). This effect was apparent in both left and right dLGN.
Conclusions: :
Melanopsin promotes ocular segregation of retinogeniculate afferents in mouse pups reared in constant light. We have shown previously that melanopsin mediates light-driven increases in the duration of retinal-wave-associated spike bursts in conventional ganglion cells. These results imply that light, acting through melanopsin, can refine retinofugal projections in early postnatal animals before rods and cones are able to influence the ganglion cells or brain. They further suggest a novel developmental role for the centrifugal influences of melanopsin ganglion cells on other retinal neurons.
Keywords: ganglion cells • thalamus/lateral geniculate nucleus • development