title: Effects of increasing CREB-dependent transcription on the storage and recall processes in a hippocampal CA1 microcircuit.
abstract: The involvement of the hippocampus in learning processes and major brain diseases makes it an ideal candidate to investigate possible ways to devise effective therapies for memory-related pathologies like Alzheimer's Disease (AD). It has been previously reported that augmenting CREB activity increases the synaptic Long-Term Potentiation (LTP) magnitude in CA1 pyramidal neurons and their intrinsic excitability in healthy rodents. It has also been suggested that hippocampal CREB signaling is likely to be down-regulated during AD, possibly degrading memory functions. Therefore, the concept of CREB-based memory enhancers, i.e. drugs that would boost memory by activation of CREB, has emerged. Here, using a model of a CA1 microcircuit, we investigate whether hippocampal CA1 pyramidal neuron properties altered by increasing CREB activity may contribute to improve memory storage and recall. With a set of patterns presented to a network, we find that the pattern recall quality under AD-like conditions is significantly better when boosting CREB function with respect to control. The results are robust and consistent upon increasing the synaptic damage expected by AD progression, supporting the idea that the use of CREB-based therapies could provide a new approach to treat AD.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bianchi
authors.forename: Pasquale
authors.initials: P
authors.lastname: De Michele
authors.forename: Cristina
authors.initials: C
authors.lastname: Marchetti
authors.forename: Brunello
authors.initials: B
authors.lastname: Tirozzi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuomo
authors.forename: Hélène
authors.initials: H
authors.lastname: Marie
authors.forename: Michele
authors.initials: M
authors.lastname: Migliore
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology* / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism*; D003198:Computer Simulation; D006801:Humans; D011939:Mental Recall / Q000502:physiology*; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*
chemical_list: D050882:CREB-Binding Protein