title: Constitutive activation of CREB in mice enhances temporal association learning and increases hippocampal CA1 neuronal spine density and complexity.
abstract: Transcription factor CREB is believed to play essential roles in the formation of long-term memory (LTM), but not in learning and short-term memory (STM). Surprisingly, we previously showed that transgenic mice expressing a dominant active mutant of CREB (DIEDML) in the forebrain (DIEDML mice) demonstrated enhanced STM and LTM in hippocampal-dependent, rapid, one-trial learning tasks. Here we show that constitutive activation of CREB enhances hippocampal-dependent learning of temporal association in trace fear conditioning and delayed matching-to-place tasks. We then show that in DIEDML mice the apical tuft dendrites of hippocampal CA1 pyramidal neurons, required for temporal association learning, display increased spine density, especially of thin spines and of Homer1-negative spines. In contrast, the basal and apical oblique dendrites of CA1 neurons, required for rapid one-trial learning, show increased density of thin, stubby, and mushroom spines and of Homer1-positive spines. Furthermore, DIEDML mice showed increased dendritic complexity in the proximal portion of apical CA1 dendrites to the soma. In contrast, forebrain overexpression of CaMKIV, leading to enhanced LTM but not STM, show normal learning and CA1 neuron morphology. These findings suggest that dendritic region-specific morphological changes in CA1 neurons by constitutive activation of CREB may contribute to improved learning and STM.
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Tatsurou
authors.initials: T
authors.lastname: Serita
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.|Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Hotaka
authors.initials: H
authors.lastname: Fukushima
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.|Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kida
mesh_terms: D000818:Animals; D001245:Association Learning; D056547:CA1 Region, Hippocampal / Q000166:cytology* / Q000502:physiology*; D003214:Conditioning, Classical; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D049229:Dendritic Spines; D005239:Fear; D005260:Female; D008297:Male; D018782:Maze Learning; D008570:Memory, Short-Term; D051379:Mice; D017966:Pyramidal Cells / Q000166:cytology* / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein