title: Satb2 determines miRNA expression and long-term memory in the adult central nervous system.
abstract: SATB2is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.
authors.affiliation: Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Jaitner
authors.affiliation: Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Chethan
authors.initials: C
authors.lastname: Reddy
authors.affiliation: Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Abentung
authors.affiliation: Department of Pharmacology and Toxicology, University of Innsbruck, Innsbruck, Austria.
authors.forename: Nigel
authors.initials: N
authors.lastname: Whittle
authors.affiliation: Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Rieder
authors.affiliation: Zoological Institute, Technical University Braunschweig, Braunschweig, Germany.
authors.forename: Andrea
authors.identifier: 0000-0002-8887-0806
authors.initials: A
authors.lastname: Delekate
authors.affiliation: Zoological Institute, Technical University Braunschweig, Braunschweig, Germany.|AG Neuroinflammation and Neurodegeneration (NIND), Braunschweig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Korte
authors.affiliation: Research Group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Göttingen, Germany.|Research Group for Complex Neurodegenerative Disorders, German Center for Neurodegenerative Diseases, Göttingen, Germany.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Jain
authors.affiliation: Research Group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Göttingen, Germany.|Department of Psychiatry and Psychotherapy, University Medical Center, German Center for Neurodegenerative Diseases, Göttingen, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Research Group for Complex Neurodegenerative Disorders, German Center for Neurodegenerative Diseases, Göttingen, Germany.
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Sananbenesi
authors.affiliation: Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Isabella
authors.initials: I
authors.lastname: Cera
authors.affiliation: Department of Pharmacology and Toxicology, University of Innsbruck, Innsbruck, Austria.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Singewald
authors.affiliation: Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Dechant
authors.affiliation: Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Galina
authors.identifier: 0000-0003-2682-4385
authors.initials: G
authors.lastname: Apostolova
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006624:Hippocampus / Q000502:physiology*; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057567:Memory, Long-Term; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D036961:Matrix Attachment Region Binding Proteins; D035683:MicroRNAs; C501473:SATB2 protein, mouse; D014157:Transcription Factors
keywords: LTP; chromatin; chromosomes; genes; long-term memory; miRNA; mouse; neuroscience; synaptic plasticity