Mutant mice lacking ryanodine receptor type 3 exhibit deficits of contextual fear conditioning and activation of calcium/calmodulin-dependent protein kinase II in the hippocampus.
As it is known that ryanodine receptor type 3 is expressed in the hippocampus, we examined the contribution of this receptor to contextual fear conditioning behavior and to the activation of Ca(2+)/calmodulin-dependent protein kinase II using mice lacking the receptor. Ryanodine receptor type 3-deficient mice exhibited impairments of performance in the contextual fear conditioning test, passive avoidance test, and Y-maze learning test. Both the activities of Ca(2+)/calmodulin-dependent protein kinase IIbeta and Ca(2+)/calmodulin-dependent protein kinase IIalpha were significantly increased in the experimental group compared to the control group in the hippocampus, but not in the cingulate cortex on the testing day 24 h after contextual fear training. However, the activities of Ca(2+)/calmodulin-dependent protein kinase IIbeta and alpha were almost the same in the experimental and control groups in the hippocampus on the training day. Ryanodine receptor type 3-deficient mice did not show the increment of Ca(2+)/calmodulin-dependent protein kinase IIbeta and alpha activities in the hippocampus on the testing day. In addition, these mutant mice showed the reduction of fear response in the elevated plus-maze test. The present results suggest that calcium-induced calcium release through the activation of ryanodine receptor type 3 in the hippocampus is important to the expression of the performance of contextual learning through the elevation of Ca(2+)/calmodulin-dependent protein kinase IIbeta and alpha activities.
Kouzu
Y
Y
Department of Pharmacology and Brain Science, School of Human Sciences, Waseda University, Tokorozawa, Saitama, Japan.
Moriya
T
T
Takeshima
H
H
Yoshioka
T
T
Shibata
S
S
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000502:physiology*; D004789:Enzyme Activation; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000201:enzymology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
D019837:Ryanodine Receptor Calcium Release Channel; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517671:Camk2a protein, mouse; C517672:Camk2b protein, mouse