Disruption of retinogeniculate pattern formation by inhibition of soluble guanylyl cyclase.
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.
Leamey
C A
CA
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Ho-Pao
C L
CL
Sur
M
M
D000375:Aging / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005289:Ferrets; D005829:Geniculate Bodies / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles; D019581:Neuropil / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D011810:Quinoxalines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D010069:Oxadiazoles; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin; C073601:KT 5823; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D006152:Cyclic GMP