CREB required for the stability of new and reactivated fear memories.
The cAMP-responsive element binding protein (CREB) family of transcription factors is thought to be critical in memory formation. To define the role of CREB in distinct memory processes, we derived transgenic mice with an inducible and reversible CREB repressor by fusing CREBS133A to a tamoxifen (TAM)-dependent mutant of an estrogen receptor ligand-binding domain (LBD). We found that CREB is crucial for the consolidation of long-term conditioned fear memories, but not for encoding, storage or retrieval of these memories. Our studies also showed that CREB is required for the stability of reactivated or retrieved conditioned fear memories. Although the transcriptional processes necessary for the stability of initial and reactivated memories differ, CREB is required for both. The findings presented here delineate the memory processes that require CREB and demonstrate the power of LBD-inducible transgenic systems in the study of complex cognitive processes.
Kida
Satoshi
S
Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
Josselyn
Sheena A
SA
Peña de Ortiz
Sandra
S
Kogan
Jeffrey H
JH
Chevere
Itzamarie
I
Masushige
Shoichi
S
Silva
Alcino J
AJ
D000818:Animals; D001921:Brain / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D005239:Fear / Q000502:physiology*; D005786:Gene Expression Regulation; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D011993:Recombinant Fusion Proteins