CALRETININ EXPRESSION AS A CRITICAL COMPONENT IN THE CONTROL OF DENTATE GYRUS LONG-TERM POTENTIATION INDUCTION IN MICE

We have recently reported that mice homozygous (Cr-/-) for a null muta tion in the calretinin gene have impaired long-term potentiation (LTP) induction in the dentate gyrus (S, Schurmans et al. (1997) Proc. Natl . Acad. Sci. USA, 94, 10415), Here, we investigated dentate LTP induct ion in mice heterozygous (Cr+/-) for the same mutation. Despite the pr esence of calretinin in neurons of these mice, although at reduced lev els as compared with normal mice, LTP induction in dentate gyrus was t otally impaired. Spatial memory and learning were found unaffected in Cr+/- mice, such as in Cr-/- mice. Altogether, our results suggest tha t calretinin is a critical component in the control of dentate synapti c plasticity in mice, and that levels of calretinin higher than those observed in Cr+/- mice are required to induce LTP in this area. The po ssible mechanisms leading to the absence of correlation between gene d osage and biological effects are discussed.