Function of Ca^(2+)-/calmodulin-dependent protein kinase Ⅳ in Ca^(2+)-stimulated neuronal signaling and behavior

The activity of Ca2+/calmodulin-dependent protein kinase IV(Ca MKIV) is sensitive to activity-dependent changes in the level of intracellular Ca2+.Following neuronal stimulation,the activation of Ca MKIV may trigger synaptic modifications and transcriptional responses,both of which are involved in regulating cognitive and emotional behavior.Here,we used Ca MKIV knockout(KO) neurons and mice to examine the function of Ca MKIV in Ca2+-stimulated intracellular signaling and animal behavior,respectively.Following NMDA receptor activation or membrane depolarization,the up-regulation of CREB(c AMP responsive element binding protein) and its target gene Bdnf(brain-derived neurotrophic factor) was intact in cortical neurons obtained from Ca MKIV KO mice.Ca MKIV KO mice displayed severe impairment in contextual fear memory but normal locomotor activity and anxiety level in the contextual training chamber.Although Ca MKIV KO mice showed normal memory in the standard passive avoidance task,they were defective in learning the temporal dissociative passive avoidance task.As indicated by the light/dark test and marble-burying test data,Ca MKIV KO mice showed less anxiety and normal perseveration.In the voluntary wheel-running test,Ca MKIV KO mice showed normal running time and distance but higher maximal running speed.Our results demonstrate the function of Ca MKIV in regulating different forms of fear memory,anxiety,and certain aspect of motor function.