INVOLVEMENT OF GRANULE, BASKET AND STELLATE NEURONS BUT NOT PURKINJE OR GOLGI CELLS IN CEREBELLAR CGMP INCREASES IN-VIVO

Recent immunocytochemical studies of cerebellar nitric oxide synthase (NOS) and cGMP have aided dramatically in defining possible cellular s ources of cGMP generation in the signal transduction cascade evoked by excitatory amino acids in the cerebellum. Using a mouse mutant defici ent in cerebellar Purkinje cells (''nervous'' mouse) and chemical lesi ons of cerebellar neurons with methylazoxymethanol (MAM), we have exam ined in vivo generation of cGMP to determine the roles of different ce rebellar neuronal populations. In the case of ''nervous'' mice, our da ta indicate that cerebellar Purkinje cells are not required for NMDA-d ependent increases in cGMP in the cerebellum. In marked contrast, MAM lesions which reduce granule but not Golgi cells in the granule cell l ayer and reduce basket and stellate cells in the molecular layer, dram atically reduced the ability of NMDA to increase cerebellar cGMP. Thes e data support immunocytochemical data of cerebellar NOS pools and ind icate the importance of granule, basket and possibly stellate cells in the generation of nitric oxide, which in turn activates guanylate cyc lase, in a diversity of cells, to increase cerebellar cGMP levels.