title: Neural ECM molecules in synaptic plasticity, learning, and memory.
abstract: Neural extracellular matrix (ECM) molecules derived from neurons and glial cells accumulate in the extracellular space and regulate synaptic plasticity through modulation of perisomal GABAergic inhibition, intrinsic neuronal excitability, integrin signaling, and activities of L-type Ca(2+) channels, NMDA receptors, and Rho-associated kinase. Genetic or enzymatic targeting of ECM molecules proved to bidirectionally modulate acquisition of memories, depending on experimental conditions, and to promote cognitive flexibility and extinction of fear and drug memories. Furthermore, evidence is accumulating that dysregulation of ECM is linked to major psychiatric and neurodegenerative diseases and that targeting ECM molecules may rescue cognitive deficits in animal models of these diseases. Thus, the ECM emerged as a key component of synaptic plasticity, learning, and memory and as an attractive target for developing new generation of synapse plasticizing drugs.
authors.affiliation: Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
authors.forename: Oleg
authors.initials: O
authors.lastname: Senkov
authors.affiliation: Center for Laser Microscopy, Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
authors.forename: Pavle
authors.initials: P
authors.lastname: Andjus
authors.affiliation: Center for Laser Microscopy, Institute for Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Radenovic
authors.affiliation: Department of Cell Biology, University of Barcelona, Barcelona, Spain; Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, Madrid, Spain; Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Soriano
authors.affiliation: Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany; Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa, Italy; Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Magdeburg, Germany. Electronic address: alexander.dityatev@dzne.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dityatev
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
keywords: Chondroitin sulfate; ECM; Extracellular matrix; Heparan sulfate; Hyaluronic acid; Learning; Memory; Reelin; Synaptic plasticity; Tenascin