Abstract
Purpose: :
Waves of activity that sweep across the early postnatal retina help to refine developing retinofugal projections. These retinal waves occur before rod and cone circuits can drive the inner retina, but after intrinsically photosensitive retinal ganglion cells (ipRGCs) are fully competent. We wondered whether ipRGCs might permit photic modulation of the retinal waves and whether ipRGCs are influenced by the waves.
Methods: :
We recorded from ipRGCs and other retinal ganglion cells (RGCs) in early postnatal mouse retina (P4-7) using multielectrode array (MEA), loose-patch and whole-cell methods. ipRGCs were easily identifiable as the only light-responsive RGCs at this developmental stage. For patch studies, we used a melanopsin reporter mouse (opn4cre/+; Z/EG+/-) to target ipRGCs (EGFP+) or conventional RGCs (EGFP-). That mouse and a melanopsin-knockout line were kindly provided by Samer Hattar.
Results: :
Light exposure significantly increased the duration of RGC bursts during the retinal waves. Because ipRGCs are the only functional photoreceptors at this stage, they presumably mediate this photic influence. We confirmed this by showing that in melanopsin knockout mice, which lack ipRGC photosensitivity, light had no effect on the duration of wave-associated spiking. The mechanisms by which photoactivated ipRGCs increase wave duration are unclear, though pilot data in wildtype mice suggest that changes in the resting potential of conventional RGCs are not required. ipRGCs burst along with neighboring RGCs as the waves pass through. Thus, ipRGCs not only influence the waves, but are also influenced by them.
Conclusions: :
Light modulates the dynamics of retinal waves in early postnatal retinal development and may thus influence circuit maturation in the central visual system. Light effects on waves are not mediated by rods or cones, which cannot drive the inner retina at this stage, but rather by melanopsin-based phototransduction in ipRGCs. The ability of ipRGCs to modulate a global, inner-retinal process like the waves lends further weight to growing evidence that ipRGCs exert centrifugal influences on other retinal neurons.
Keywords: retinal connections, networks, circuitry • retinal development • retina: proximal (bipolar, amacrine, and ganglion cells)