Comprehensive behavioral analysis of calcium/calmodulin-dependent protein kinase IV knockout mice

• Published in: PloS one 2010-03, Vol.5 (3), p.e9460-e9460
• Main Authors: Takao, Keizo, Tanda, Koichi, Nakamura, Kenji, Kasahara, Jiro, Nakao, Kazuki, Katsuki, Motoya, Nakanishi, Kazuo, Yamasaki, Nobuyuki, Toyama, Keiko, Adachi, Minami, Umeda, Masahiro, Araki, Tsutomu, Fukunaga, Kohji, Kondo, Hisatake, Sakagami, Hiroyuki, Miyakawa, Tsuyoshi
• Format: Article
• Language: English
• Subjects: Animals; Anxiety; Batteries; Behavior, Animal; Behavioral plasticity; Ca2+/calmodulin-dependent protein kinase IV; Calcium; Calcium binding proteins; Calcium-binding protein; Calcium-Calmodulin-Dependent Protein Kinase Type 4 - genetics; Calmodulin; Cell Biology/Neuronal Signaling Mechanisms; Consolidation; Crosses, Genetic; Cyclic adenosine monophosphate; Cyclic AMP; Cyclic AMP response element-binding protein; Depression - genetics; Emotional behavior; Fear; Fear conditioning; Female; Genetic engineering; Inhibition (psychology); Kinases; Locomotor activity; Male; Maze Learning; Memory; Memory tasks; Mental depression; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Motor Skills; Mutation; Neurological Disorders/Neuropsychiatric Disorders; Neuroscience/Behavioral Neuroscience; Pain; Pain sensitivity; Protein binding; Protein kinases; Rodents; Short term memory; Signaling; Social aspects; Social behavior; Spatial analysis; Spatial Behavior; Spatial discrimination learning; Spatial memory; Synaptic plasticity; Training
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009460

Calcium-calmodulin dependent protein kinase IV (CaMKIV) is a protein kinase that activates the transcription factor CREB, the cyclic AMP-response element binding protein. CREB is a key transcription factor in synaptic plasticity and memory consolidation. To elucidate the behavioral effects of CaMKIV deficiency, we subjected CaMKIV knockout (CaMKIV KO) mice to a battery of behavioral tests. CaMKIV KO had no significant effects on locomotor activity, motor coordination, social interaction, pain sensitivity, prepulse inhibition, attention, or depression-like behavior. Consistent with previous reports, CaMKIV KO mice exhibited impaired retention in a fear conditioning test 28 days after training. In contrast, however, CaMKIV KO mice did not show any testing performance deficits in passive avoidance, one of the most commonly used fear memory paradigms, 28 days after training, suggesting that remote fear memory is intact. CaMKIV KO mice exhibited intact spatial reference memory learning in the Barnes circular maze, and normal spatial working memory in an eight-arm radial maze. CaMKIV KO mice also showed mildly decreased anxiety-like behavior, suggesting that CaMKIV is involved in regulating emotional behavior. These findings indicate that CaMKIV might not be essential for fear memory or spatial memory, although it is possible that the activities of other neural mechanisms or signaling pathways compensate for the CaMKIV deficiency.