Expression of soluble guanylyl cyclase in rat cerebral cortex during postnatal development

Soluble guanylyl cyclase (sGC), the principle "receptor" for nitric oxide (NO), catalyzes the formation of cyclic guanosine monophosphate (cGMP), an intracellular second messenger. Studies in invertebrates have shown that the NO/cGMP pathway is involved in several aspects of neural development, including neuronal migration, dendritic and axonal outgrowth, and synaptogenesis. In vitro studies suggest a developmental role also in mammals. To investigate whether the NO/cGMP pathway might mediate these processes in vivo, we performed immunohistochemistry for sGC on sections from postnatal rat cerebral cortex. Early in postnatal development, migrating neurons in the cortical plate were immunonegative, whereas neurons deeper in the cortex that had completed migration were immunopositive. At the subcellular level, sGC preferentially stained dendrites rather than axons, but, at postnatal day 1 (PND1), sGC was found in a large fraction of axonal growth cones, especially those oriented toward the pial surface. At PND10-20 (the period of maximal synaptogenesis), sGC immunostaining was located mainly in dendritic shafts and was only occasionally associated with spines or axon terminals. These results support a role for the NO/cGMP pathway in dendritic development but argue against a major role in neuronal migration and synaptogenesis.