title: Increased Sparsity of Hippocampal CA1 Neuronal Ensembles in a Mouse Model of Down Syndrome Assayed by Arc Expression.
abstract: Down syndrome (DS) is the leading chromosomal cause of intellectual disability, yet the neural substrates of learning and memory deficits remain poorly understood. Here, we interrogate neural networks linked to learning and memory in a well-characterized model of DS, the Ts65Dn mouse. We report that Ts65Dn mice exhibit exploratory behavior that is not different from littermate wild-type (WT) controls yet behavioral activation of Arc mRNA transcription in pyramidal neurons of the CA1 region of the hippocampus is altered in Ts65Dn mice. In WT mice, a 5 min period of exploration of a novel environment resulted in Arc mRNA transcription in 39% of CA1 neurons. By contrast, the same period of exploration resulted in only ~20% of CA1 neurons transcribing Arc mRNA in Ts65Dn mice indicating increased sparsity of the behaviorally induced ensemble. Like WT mice the CA1 pyramidal neurons of Ts65Dn mice reactivated Arc transcription during a second exposure to the same environment 20 min after the first experience, but the size of the reactivated ensemble was only ~60% of that in WT mice. After repeated daily exposures there was a further decline in the size of the reactivated ensemble in Ts65Dn and a disruption of reactivation. Together these data demonstrate reduction in the size of the behaviorally induced network that expresses Arc in Ts65Dn mice and disruption of the long-term stability of the ensemble. We propose that these deficits in network formation and stability contribute to cognitive symptoms in DS.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of MedicineBaltimore, MD, USA; Department of Neurology, Johns Hopkins University School of MedicineBaltimore, MD, USA.
authors.forename: Constance L
authors.initials: CL
authors.lastname: Smith-Hicks
authors.affiliation: The State Key Laboratory of Biotherapy, West-China Hospital, Sichuan University Chengdu, China.
authors.forename: Peiling
authors.initials: P
authors.lastname: Cai
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine Baltimore, MD, USA.
authors.forename: Alena V
authors.initials: AV
authors.lastname: Savonenko
authors.affiliation: Department of Physiology and Institute of Genetic Medicine, Johns Hopkins University, School of Medicine Baltimore, MD, USA.
authors.forename: Roger H
authors.initials: RH
authors.lastname: Reeves
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of MedicineBaltimore, MD, USA; Department of Neurology, Johns Hopkins University School of MedicineBaltimore, MD, USA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Worley
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000378:metabolism / Q000503:physiopathology*; D005106:Exploratory Behavior / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D009415:Nerve Net / Q000378:metabolism / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein
keywords: Arc/Arg3.1; activity regulated cytoskeletal protein; catFISH; learning and memory; neural-networks