Comprehensive behavioral analysis of calcium/calmodulin-dependent protein kinase IV knockout mice.
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.
Takao
Keizo
K
Genetic Engineering and Functional Genomics Group, Frontier Technology Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Tanda
Koichi
K
Nakamura
Kenji
K
Kasahara
Jiro
J
Nakao
Kazuki
K
Katsuki
Motoya
M
Nakanishi
Kazuo
K
Yamasaki
Nobuyuki
N
Toyama
Keiko
K
Adachi
Minami
M
Umeda
Masahiro
M
Araki
Tsutomu
T
Fukunaga
Kohji
K
Kondo
Hisatake
H
Sakagami
Hiroyuki
H
Miyakawa
Tsuyoshi
T
D000818:Animals; D001522:Behavior, Animal; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000235:genetics*; D003433:Crosses, Genetic; D003863:Depression / Q000235:genetics; D005260:Female; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009048:Motor Skills; D013037:Spatial Behavior
D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4