Dentate gyrus-specific manipulation of beta-Ca2+/calmodulin-dependent kinase II disrupts memory consolidation.
Although the functions of alpha-Ca(2+)/calmodulin-dependent kinase II (CaMKII) have been studied extensively, the role of betaCaMKII, a coconstituent of the CaMKII holoenzyme in synaptic plasticity, learning, and memory has not been examined in vivo. Here we produce a transgenic mouse line in which the inducible and reversible manipulation of betaCaMKII activity is restricted to the hippocampal dentate gyrus, the region where long-term potentiation was originally discovered. We demonstrate that betaCaMKII activity in the dentate gyrus selectively impaired long-term potentiation in the dentate perforant path, but not in the CA1 Schaffer collateral pathway. Although the transgenic mice showed normal 1-day memories, they were severely impaired in 10-day contextual fear memory. Systematic manipulations of dentate betaCaMKII activity during various distinct memory stages further reveal the initial day within the postlearning consolidation period as a critical time window that is highly sensitive to changes in betaCaMKII activity. This study provides evidence not only for the functional role of betaCaMKII in the dentate gyrus plasticity and hippocampal memory, but also for the notion that the mismatch between the actual learning pattern and reactivation patterns in the dentate gyrus circuit can underlie long-term memory consolidation.
Cho
Min H
MH
Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA.
Cao
Xiaohua
X
Wang
Deheng
D
Tsien
Joe Z
JZ
D000595:Amino Acid Sequence; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018891:Dentate Gyrus / Q000201:enzymology* / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology; D008568:Memory / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D010597:Pharmacogenetics; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2