The distribution of nitric oxide synthase-I and NADPH-diaphorase containing neurons in the cerebral cortex of different strains of mice and its association with learning and memory.

We investigated the distribution of nitric oxide synthase-I (NOS-I) containing neurons within the neocortex of inbred mice belonging to the Balb/c, NMRI and DBA/2 strains which differ in learning and memory performance. The NOS-I positive neurons were detected immunohistochemically with antibodies against NOS-I and enzyme histochemically using their NADPH-diaphorase (NADPH-d) activity. The qualitative and quantitative evaluation of cortical NADPH-d and NOS-I containing neurons revealed that more than 95% of these cells contained both enzymes. Therefore, we combined the NADPH-d with the WFA-staining to evaluate and parcellate at one section. The specific differences in learning and memory tasks of the three mouse strains have been tested in previous studies. Our investigation test the hypothesis that differences in various aspects of eight-arm radial maze learning are associated with differences in the density of NOS-I positive neurons in cytoarchitectonically and functionally identified cortical areas. We found an increased density of NADPH-d neurons within the whole neocortex in the DBA/2 strain, which reached a lower learning score than the Balb/c and NMRI strains. Significantly higher densities of NADPH-d neurons appeared in the areas of the gustatory cortex, the piriform cortex, the entorhinal cortex and in area 1 of the temporal cortex in DBA/2 mice. A negative correlation exists between the learning scores and the number of NADPH-d positive neurons. If NOS-I activity influences spatial learning as determined in the eight-arm radial maze, the areas with strongly elevated NADPH-d positive neurons may demarcate task-related cortical areas affected in mice with a reduced learning capacity.