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The Journal of Neuroscience, June 1, 2001, 21(11):3871-3880

Disruption of Retinogeniculate Pattern Formation by Inhibition of Soluble Guanylyl Cyclase

Catherine A. Leamey, Chrystal L. Ho-Pao, and Mriganka Sur

Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

During development of the visual system of the ferret, the terminals of retinal ganglion cell axons first segregate to form eye-specific layers and subsequently On-center and Off-center sublayers within the dorsal lateral geniculate nucleus (dLGN). Sublamination requires the activity of the afferent fibers, NMDA receptors, and nitric oxide synthase (NOS). We here report that soluble guanylyl cyclase (sGC), which in turn produces cGMP, is critically involved in the process of sublamination. cGMP expression is upregulated in both retinal terminals and postsynaptic dLGN cells during sublamination, and this expression is controlled by the activity of both NMDA receptors and NOS. Furthermore, the infusion of specific inhibitors of sGC or protein kinase G (PKG), a target of cGMP, prevents sublamination in vivo. We conclude that the sGC-cGMP-PKG pathway acts downstream of NMDA receptors and nitric oxide as an effector of the activity-dependent refinement of connections at this level of the mammalian visual system.

Key words: visual system development; ferret; lateral geniculate nucleus; activity; NMDA receptors; nitric oxide; soluble guanylyl cyclase; cGMP

Copyright © 2001 Society for Neuroscience  0270-6474/01/21113871-10$05.00/0


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