title: The memory gene KIBRA is a bidirectional regulator of synaptic and structural plasticity in the adult brain.
abstract: Memory formation is associated with activity-dependent changes in synaptic plasticity. The mechanisms underlying these processes are complex and involve multiple components. Recent work has implicated the protein KIBRA in human memory, but its molecular functions in memory processes remain not fully understood. Here, we show that a selective overexpression of KIBRA in neurons increases hippocampal long-term potentiation (LTP) but prevents the induction of long-term depression (LTD), and impairs spatial long-term memory in adult mice. KIBRA overexpression increases the constitutive recycling of AMPA receptors containing GluA1 (GluA1-AMPARs), and favors their activity-dependent surface expression. It also results in dramatic dendritic rearrangements in pyramidal neurons both in vitro and in vivo. KIBRA knockdown in contrast, abolishes LTP, decreases GluA1-AMPARs recycling and reduces dendritic arborization. These results establish KIBRA as a novel bidirectional regulator of synaptic and structural plasticity in hippocampal neurons, and of long-term memory, highly relevant to cognitive processes and their pathologies.
authors: Laboratory of Neuroepigenetics, Medical Faculty of the University of Zürich and Department of Health Science and Technology of the Swiss Federal Institute of Technology Zürich, Brain Research Institute, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors: Fabrice D
authors: FD
authors: Heitz
authors: Laboratory of Neuroepigenetics, Medical Faculty of the University of Zürich and Department of Health Science and Technology of the Swiss Federal Institute of Technology Zürich, Brain Research Institute, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors: Mélissa
authors: M
authors: Farinelli
authors: Laboratory of Neuroepigenetics, Medical Faculty of the University of Zürich and Department of Health Science and Technology of the Swiss Federal Institute of Technology Zürich, Brain Research Institute, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors: Safa
authors: S
authors: Mohanna
authors: Laboratory of Neuroepigenetics, Medical Faculty of the University of Zürich and Department of Health Science and Technology of the Swiss Federal Institute of Technology Zürich, Brain Research Institute, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors: Martin
authors: M
authors: Kahn
authors: Internal Medicine D, Molecular Nephrology, University Hospital Münster, Domagkstrasse 3a, D-48149 Münster, Germany.
authors: Kerstin
authors: K
authors: Duning
authors: Division of Psychiatry Research, Medical Faculty of the University of Zürich, August Forel Strasse 1, CH-8008 Zürich, Switzerland.
authors: Marco C
authors: MC
authors: Frey
authors: Medizinische Klinik und Poliklinik D, Molecular Nephrology, University of Münster, Domagkstrasse 3a, D-48149 Münster, Germany.
authors: Hermann
authors: H
authors: Pavenstädt
authors: Laboratory of Neuroepigenetics, Medical Faculty of the University of Zürich and Department of Health Science and Technology of the Swiss Federal Institute of Technology Zürich, Brain Research Institute, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. Electronic address: mansuy@hifo.uzh.ch.
authors: Isabelle M
authors: IM
authors: Mansuy
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008569:Memory Disorders / Q000378:metabolism*; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D010750:Phosphoproteins; D018091:Receptors, AMPA / Q000378:metabolism*; D065852:Spatial Memory / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D018091:Receptors, AMPA; C539495:Wwc1 protein, mouse
keywords: GluA1; LTP; Neurons