Loss of Ca2+/calmodulin kinase kinase beta affects the formation of some, but not all, types of hippocampus-dependent long-term memory.
Long-term memory (LTM) requires activation of the transcription factor cAMP-responsive element binding protein (CREB). Signaling by the Ca2+/calmodulin (CaM) kinase cascade has been implicated in CREB activation and memory consolidation processes in the hippocampus. The CaM kinase kinase beta isoforms belong to the CaM kinase cascade, and we have generated null mutant mice to investigate the role of these kinases in several forms of learning and memory. The null mutants were impaired in spatial training-induced CREB activation and spatial memory formation. Furthermore, the mutants lacked late, but not early, long-term potentiation at the hippocampal CA1 synapse, and they were impaired in LTM, but not short-term memory, for the social transmission of food preferences. We suggest that the CaM kinase kinasebeta isoforms are required for the formation of hippocampal LTM. Surprisingly, however, these kinases were not needed for contextual, trace fear, and passive avoidance LTM. Our results demonstrate that different signaling processes underlie the formation of these types of hippocampal LTM.
Wolfson Institute for Biomedical Research, University College London, London, WC1E 6BT, United Kingdom.
Marco
M
Peters
Keiko
K
Mizuno
Laurence
L
Ris
Marco
M
Angelo
Emile
E
Godaux
K Peter
KP
Giese
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology / Q000502:physiology*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D008568:Memory / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology; D013995:Time
D017362:Cyclic AMP Response Element-Binding Protein; D007527:Isoenzymes; D017346:Protein Serine-Threonine Kinases; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; C517700:Camkk2 protein, mouse