title: CREB selectively controls learning-induced structural remodeling of neurons.
abstract: The modulation of synaptic strength associated with learning is post-synaptically regulated by changes in density and shape of dendritic spines. The transcription factor CREB (cAMP response element binding protein) is required for memory formation and in vitro dendritic spine rearrangements, but its role in learning-induced remodeling of neurons remains elusive. Using transgenic mice conditionally expressing a dominant-negative CREB (CREBS133A: mCREB) mutant, we found that inhibiting CREB function does not alter spine density, spine morphology, and levels of polymerized actin in naive CA1 neurons. CREB inhibition, however, impaired contextual fear conditioning and produced a learning-induced collapse of spines associated with a blockade of learning-dependent increase in actin polymerization. Blocking mCREB expression with doxycycline rescued memory and restored a normal pattern of learning-induced spines, demonstrating that CREB controls structural adaptations of neurons selectively involved in memory formation.
authors: CNR-National Research Council, Rome 00143, Italy. s.middei@hsantalucia.it
authors: Silvia
authors: S
authors: Middei
authors: Alida
authors: A
authors: Spalloni
authors: Patrizia
authors: P
authors: Longone
authors: Christopher
authors: C
authors: Pittenger
authors: Shane M
authors: SM
authors: O'Mara
authors: Hélène
authors: H
authors: Marie
authors: Martine
authors: M
authors: Ammassari-Teule
mesh_terms: D000409:Alanine / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D050882:CREB-Binding Protein / Q000235:genetics / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D003213:Conditioning, Psychological / Q000502:physiology*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology; D004597:Electroshock / Q000009:adverse effects; D005239:Fear / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D012694:Serine / Q000235:genetics; D016622:Silver Staining
chemical_list: D012694:Serine; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517671:Camk2a protein, mouse; D004318:Doxycycline; D000409:Alanine