Acute blockade of nitric oxide synthesis induces disorganization and amplifies lesion-induced plasticity in the rat retinotectal projection

In the rat visual system, the uncrossed retinotectal projection undergoes a topographical refinement within the first two postnatal weeks. We have stu died the role of nitric oxide (NO), a retrograde messenger which couples pr e- and postsynaptic activation, in the development of the uncrossed retinot ectal projection and in the plasticity of this pathway as a result of a res tricted retinal lesion in the opposite eye. During development, maximal nit ric oxide synthase (NOS) activity was observed in homogenates of tectal tis sue at postnatal day 5 (PND 5), followed by a two-step decrease at the end of the topographical fine tuning period (PND 21) and the adult stage (PND 4 2), We also tested the effects of an acute in vivo blockade of NOS during t he development of both animals that had not been operated on, and lesioned animals. Animals ranging from PND 4 to PND 42 were treated either with the NOS inhibitor, L-nitro-arginine (Narg 50 mg/kg ip.) or vehicle (NaCl 0.9%) during 4 days (from PND 4-7 or PND 9-12) or 8 days (from PND 20-27 or PND 3 4-41), Reduction of NOS activity induced sprouting of the ipsilateral pathw ay up to the second postnatal week in the animals that had not been operate d on. Rats that had been operated on, however, showed an amplification of t he lesion-induced plasticity up to the fourth postnatal week under NOS bloc kade. The data suggest that NO plays a role in the stabilization of retinot ectal synapses during the critical period of topographic refinement, and in dicate that an acute blockade of retrograde signals enables plastic rearran gements in the visual system within this time window. (C) 2000 John Wiley & Sons, Inc.