Nitric oxide, impulse activity, and neurotrophins in visual system development

Topographic refinement of synaptic connections within the developing visual system involves a variety of molecules which interact with impulse activit y in order to produce the precise retinotopic maps found in the adult brain . Nitric oxide (NO) has been implicated in this process, as have various gr owth factors. Within the subcortical visual system, we have recently shown that nitric oxide contributes to pathway refinement in the superior collicu lus (SC). Long-term potentiation (LTP) and long-term depression (LTD) are a lso expressed in SC during the time that this pathway undergoes refinement. The role of NO has been demonstrated by showing that refinement of ipsilat eral fibers in the retinocollicular pathway is significantly delayed in gen e knockout mice in which both the endothelial and neuronal isoforms of nitr ic oxide synthase (NOS) have been disrupted. The effect also depends upon C a2+ channels because refinement of both the ipsilateral retinocollicular an d retinogeniculate pathways is disrupted in genetic mutants in which the be ta3 subunit of the Ca2+ channel has been deleted. LTD may also be involved in this process, because the time course of its expression correlates with that of pathway refinement and LTD magnitude is depressed by nitrendipine, an L-type Ca2+ channel blocker. LTP is also expressed during early postnata l development in the LGN and SC and may contribute to synaptic stabilizatio n. The role of neurotrophins in pathway refinement in the visual system is also reviewed. (C) 2000 Elsevier Science B.V. All rights reserved.