title: Altered hippocampal information coding and network synchrony in APP-PS1 mice.
abstract: β-amyloid is hypothesized to harm neural function and cognitive abilities by perturbing synaptic transmission and plasticity in Alzheimer's disease (AD). To assess the impact of this pathology on hippocampal neurons' ability to encode flexibly environmental information across learning, we performed electrophysiological recordings of CA1 hippocampal unit activity in AD transgenic mice as they acquired an action-reward association in a spatially defined environment; the behavioral task enabled the precise timing of discrete and intentional behaviors of the animal. We found that the proportion of behavioral task-sensitive cells in wild-type (WT) mice typically increased, whereas the proportion of place cells decreased with learning. In AD mice, this learning-dependent change of cell-discharge patterns was absent, and cells exhibited similar firings from the beginning to firings attained at the late learning stage in wild-type cells. These inflexible hippocampal representations of task and space throughout learning are accompanied by remarkable alterations of local oscillatory activity in the theta and ultra-fast ripple frequencies as well as learning abilities. The present data offer new insights into the in vivo cellular and network processes by which β-amyloid and other AD mutations may exert its harmful effects to produce cognitive and behavioral impairments in early stage of AD.
authors.affiliation: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS UMR 5287 Pessac Cedex, France; University of Bordeaux, Pessac Cedex, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Cayzac
authors.affiliation: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS UMR 5287 Pessac Cedex, France; University of Bordeaux, Pessac Cedex, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mons
authors.affiliation: Laboratoire INSERM, UMR 894-Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; Service de Biochimie, Hôpitaux Universitaires Paris-Centre, Hôpital Cochin, AP-HP, Paris, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Ginguay
authors.affiliation: Laboratoire INSERM, UMR 894-Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Allinquant
authors.affiliation: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS UMR 5287 Pessac Cedex, France; University of Bordeaux, Pessac Cedex, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Jeantet
authors.affiliation: Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS UMR 5287 Pessac Cedex, France; University of Bordeaux, Pessac Cedex, France. Electronic address: yoon.cho@u-bordeaux1.fr.
authors.forename: Yoon H
authors.initials: YH
authors.lastname: Cho
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology* / Q000523:psychology*; D000818:Animals; D001522:Behavior, Animal; D056547:CA1 Region, Hippocampal / Q000503:physiopathology*; D003071:Cognition; D055724:Electrophysiological Phenomena; D007858:Learning; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos; D012201:Reward; D013037:Spatial Behavior; D013826:Theta Rhythm / Q000502:physiology*
chemical_list: D016760:Proto-Oncogene Proteins c-fos
keywords: APP-PS1 mice; Alzheimer's disease; Cognition; Place cell; Ripple oscillation; Synaptic plasticity; Theta synchrony; c-Fos; β-amyloid