Initial studies on Kal7KO mice confirmed a role for Kal7/ΔKal7 in nervous system function [12,17]. A slight decrease in linear spine density on CA1 hippocampal pyramidal neurons is accompanied by a decrease in spontaneous EPSP frequency and deficient hippocampal LTP [17]. In contrast, spine density is normal in the Kal7KO NAc under basal conditions [12]. Although chronic administration of cocaine increases spine density on the medium spiny neurons in the NAc [35,42,65], this response is absent in Kal7KO mice [12]. The behavioral responses of Kal7KO mice to chronic cocaine are also altered [12]. Levels of both Cdk5 and NR2B, which play essential roles in the structural and behavioral responses to cocaine [17,30,41,66-69], are diminished in PSDs prepared from the cortices of Kal7KO mice. A similar relationship between Kal7 and Cdk5 and NR2B in the NAc may contribute to the behavioral deficits observed.
