An important role of neural activity-dependent CaMKIV signaling in the consolidation of long-term memory.
Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has been implicated in the regulation of CRE-dependent transcription. To investigate the role of this kinase in neuronal plasticity and memory, we generated transgenic mice in which the expression of a dominant-negative form of CaMKIV (dnCaMKIV) is restricted to the postnatal forebrain. In these transgenic mice, activity-induced CREB phosphorylation and c-Fos expression were significantly attenuated. Hippocampal late LTP (L-LTP) was also impaired, whereas basic synaptic function and early LTP (E-LTP) were unaffected. These deficits correlated with impairments in long-term memory, specifically in its consolidation/retention phase but not in the acquisition phase. These results indicate that neural activity-dependent CaMKIV signaling in the neuronal nucleus plays an important role in the consolidation/retention of hippocampus-dependent long-term memory.
Kang
H
H
Howard Hughes Medical Institute, New Haven, CT 06511, USA.
Sun
L D
LD
Atkins
C M
CM
Soderling
T R
TR
Wilson
M A
MA
Tonegawa
S
S
D019943:Amino Acid Substitution; D000818:Animals; D001921:Brain / Q000502:physiology*; D019556:COS Cells; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008156:Luciferases / Q000235:genetics; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology*; D016548:Prosencephalon / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
D017362:Cyclic AMP Response Element-Binding Protein; D011994:Recombinant Proteins; D008156:Luciferases; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517685:Camk4 protein, mouse