The developmental expression of neuronal nitric oxide synthase in cerebellar granule cells is sensitive to GABA and neurotrophins

In the adult cerebellar cortex, the differential expression of neuronal nitric oxide synthase (nNOS) can be used to discern discrete subsets of granule neurons. These subsets originate concurrently with the afferent innervation of granule neurons. Using primary cultures established from murine cerebella at different development stages, we analyzed the effects of the neurotransmitter GABA and the neurotrophins BDNF and NT-3 on nNOS expression in developing granule cells. We show a biophasic effect of GABA on nNOS expression, which correlates with the ability of this transmitter to increase intracellular calcium levels. BDNF and NT-3 are shown to increase nNOS levels in cultures derived from postnatal, but not in those from embryonic cerebella. Together with previous findings [Baader and Schilling; J Neurosci 1996;16:1440-1449], these data suggest a scenario in which afferent innervation and growth factors cooperate to differentially affect nNOS expression at discrete developmental stages of cerebellar granule cells.