DISTINCTIONS BETWEEN HIPPOCAMPUS OF MOUSE AND RAT - PROTEIN F1 GAP-43GENE-EXPRESSION, PROMOTER ACTIVITY, AND SPATIAL MEMORY/

We began these experiments as an attempt to replicate in the mouse the induction by kainate (KA) of F1/GAP-43 mRNA we observed in adult rat hippocampal granule cells [Mol. Brain Res., 33 (1995) 22-28]. However, even though KA induced behavioral seizures in the mouse similar to th ose in the rat, neither induction of F1/GAP-43 mRNA nor subsequent mos sy fiber sprouting observed in the rat was detected in three different mouse strains. It was also surprising that the distribution of consti tutive levels of F1/GAP-43 mRNA in mouse and rat hippocampus was quali tatively different. Indeed, F1/GAP-43 expression in CA3 pyramidal cell s was significantly greater in rat than mouse, while F1/GAP-43 express ion in CA1 cells of rat and mouse was equivalent using densitometric a nalysis. Thus, F1/GAP-43 expression in rat is quantitatively higher in CA3 than CA1 pyramidal cells. In mouse, expression was equivalent in these two subfields. In a transgenic mouse bearing a rat F1/GAP-43 pro moter-reporter (lacZ) construct (line 252), in-vivo promoter activity of F1/CAP-43 was studied in hippocampal cells. Transgene expression in hippocampal pyramidal subfields, high in CA3, low in CA1 pyramidal ce lls, paralleled the distribution of rat F1/GAP-43 mRNA levels, not mou se. Differences in the constitutive F1/GAP-43 expression pattern in hi ppocampus between rat and mouse may therefore be determined by differe nt recognition elements present on the F1/GAP-43 promoter. KA injected into the line 252 transgenic mouse did not activate the rat F1/GAP-43 promoter in mouse hippocampal granule cells. The absence of both F1/G AP-43 mRNA expression induction and promoter activation in mouse granu le cells after KA is likely related to genera differences in transcrip tional regulatory mechanisms, though post-transcriptional mechanisms c annot be excluded. Since the different hippocampal chemistry of F1/GAP -43 in rat and mouse likely extends to other molecular species, behavi ors in rat and mouse that depend on hippocampal function might be diff erent as well. We therefore evaluated spatial memory ability in a dela yed matching-to-sample task. In contrast to rat, we were surprised to find no evidence of the ability to learn this task in three different mouse strains. Since interest in mouse genetics in relation to behavio r and memory functions of hippocampus is,stowing, generalizations conc erning hippocampal function from studies carried out on the mouse need to be made with caution considering the specific behavioral, pharmaco logical, and general molecular differences observed here. One can also be opportunistic and exploit the natural variations between these two genera to gain insight into the molecular mechanisms underlying infor mation storage.