Abnormal fear response and aggressive behavior in mutant mice deficient for alpha-calcium-calmodulin kinase II

Mice deficient for the gene encoding α-calcium-calmodulin-dependent kinase II (α-CaMKII knockout mice) provide a promising tool to link behavioral and cellular abnormalities with a specific molecular lesion. The heterozygous mouse exhibited a well-circumscribed syndrome of behavioral abnormalities, consisting primarily of a decreased fear response 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 level, both extracellular and whole-cell patch clamp recordings indicated that serotonin release in putative serotonergic neurons of the dorsal raphe was reduced. Thus, α-CaMKII knockout mice, in particular the heterozygote, may provide a model for studying the molecular and cellular basis underlying emotional disorders involving fear and aggression.
The recently developed mouse gene knockout technology has allowed us to use a multidisciplinary approach to analyze neurobiological abnormalities at the behavioral and cellular levels. Here we tested mutant mice, [...]