CA1 LONG-TERM POTENTIATION IS DIMINISHED BUT PRESENT IN HIPPOCAMPAL SLICES FROM ALPHA-CAMKII MUTANT MICE

Previous work has shown that mice missing the alpha-isoform of calcium -calmodulin-dependent protein kinase II (alpha-CaMKII) have a deficien cy in CAI hippocampal long-term potentiation (LTP). Follow-up studies on subsequent generations of these mutant mice in a novel inbred backg round by our laboratories have shown that whereas a deficiency in CA1 LTP is still present in alpha-CaMKII mutant mice, it is different both quantitatively and qualitatively from the deficiency first described. Mice of a mixed 129SvOla/SvJ;BALB/c;C57B1/6 background derived from b rother/sister mating of the alpha-CaMKII mutant line through multiple generations >10) were produced by use of in vitro fertilization. Altho ugh LTP at 60 min post-tetanus was clearly deficient in these (-/-) (a lpha-CaMKII mice (42.6%, n = 33) compared with (+/+) alpha-CaMKII cont rol animals (81.7%, n=17), alpha-CaMKII mutant mice did show a signifi cant level of LTP. The amount of LTP observed in alpha-CaMKII mutants was normally distributed, blocked by APV (2.7%, n = 8), and did not co rrelate with age. Although this supports a role for alpha-CaMKII in CA 1 LTP, it also suggests that a form of alpha-CaMKII-independent LTP is present in mice that could be dependent on another kinase, such as th e beta-isoform of CaMKII. A significant difference in input/output cur ves was also observed between (-/-) alpha-CaMKII and (+/+) (alpha-CaMK II animals, suggesting that differences in synaptic transmission may b e contributing to the LTP deficit in mutant mice. However, tetani of i ncreasing frequency (50, 100, and 200 Hz) did not reveal a higher thre shold for potentiation in (-/-) alpha-CaMKII mice compared with (+/+) alpha-CaMKII controls.