Enhanced hippocampal CA1 LTP but normal spatial learning in inositol 1,4,5-trisphosphate 3-kinase(A)-deficient mice.
To define the physiological role of IP(3)3-kinase(A) in vivo, we have generated a mouse strain with a null mutation of the IP(3)3-kinase(A) locus by gene targeting. Homozygous mutant mice were fully viable, fertile, apparently normal, and did not show any morphological anomaly in brain sections. In the mutant brain, the IP4 level was significantly decreased whereas the IP3 level did not change, demonstrating a major role of IP(3)3-kinase(A) in the generation of IP4. Nevertheless, no significant difference was detected in the hippocampal neuronal cells of the wild-type and the mutant mice in the kinetics of Ca2+ regulation after glutamate stimulation. Electrophysiological analyses carried out in hippocampal slices showed that the mutation significantly enhanced the LTP in the hippocampal CA1 region, but had no effect on the LTP in dentate gyrus (DG). No difference was noted, however, between the mutant and the wild-type mice in the Morris water maze task. Our results indicate that IP(3)3-kinase(A) may play an important role in the regulation of LTP in hippocampal CA1 region through the generation of IP4, but the enhanced LTP in the hippocampal CA1 does not affect spatial learning and memory.
Jun
K
K
National Creative Research Initiatives Center for Calcium and Learning and Department of Life Science, Pohang University of Science and Technology, Korea.
Choi
G
G
Yang
S G
SG
Choi
K Y
KY
Kim
H
H
Chan
G C
GC
Storm
D R
DR
Albert
C
C
Mayr
G W
GW
Lee
C J
CJ
Shin
H S
HS
D000818:Animals; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D003433:Crosses, Genetic; D006579:Heterozygote; D006624:Hippocampus / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D017966:Pyramidal Cells / Q000502:physiology; D015183:Restriction Mapping; D013028:Space Perception / Q000502:physiology
D007295:Inositol Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D019869:Phosphatidylinositol 3-Kinases; D002118:Calcium