ABNORMAL FEAR RESPONSE AND AGGRESSIVE-BEHAVIOR IN MUTANT MICE DEFICIENT FOR ALPHA-CALCIUM-CALMODULIN KINASE-II

Mice deficient for the gene encoding alpha-calcium-calmodulin-dependen t kinase II (alpha-CaMKII knockout mice) provide a promising tool to l ink behavioral and cellular abnormalities with a specific molecular le sion. The heterozygous mouse exhibited a well-circumscribed syndrome o f behavioral abnormalities, consisting primarily of a decreased fear r esponse and an increase in defensive aggression, in the absence of any measured cognitive deficits. Unlike the heterozygote, the homozygote displayed abnormal behavior in all paradigms tested. At the cellular l evel, both extracellular and whole-cell patch clamp recordings indicat ed that serotonin release in putative serotonergic neurons of the dors al raphe was reduced. Thus, alpha-CaMKII knockout mice, in particular the heterozygote, may provide a model for studying the molecular and c ellular basis underlying emotional disorders involving fear and aggres sion.