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The activity of Ca2+/calmodulin-dependent protein kinase Ⅳ (CaMKIV) is sensitive to activity-dependent changes in the level of intracellular Ca2+.Following neuronal stimulation, the activation of CaMKIV may trigger synaptic modifications and transcriptional responses, both of which are involved in regulating cognitive and emotional behavior.Here, we used CaMKIV knockout (KO) neurons and mice to examine the function of CaMKIV in Ca2+-stimulated intracellular signaling and animal behavior, respectively.Following NMDA receptor activation or membrane depolarization, the up-regulation of CREB (cAMP responsive element binding protein) and its target gene Bdnf (brain-derived neurotrophic factor) was intact in cortical neurons obtained from CaMKIV KO mice.