title: The neuron-specific chromatin regulatory subunit BAF53b is necessary for synaptic plasticity and memory.
abstract: Recent exome sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several human intellectual disabilities and cognitive disorders. However, it is currently unknown how mutations in BAF complexes result in impaired cognitive function. Postmitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Mice harboring selective genetic manipulations of BAF53b have severe defects in long-term memory and long-lasting forms of hippocampal synaptic plasticity. We rescued memory impairments in BAF53b mutant mice by reintroducing BAF53b in the adult hippocampus, which suggests a role for BAF53b beyond neuronal development. The defects in BAF53b mutant mice appeared to derive from alterations in gene expression that produce abnormal postsynaptic components, such as spine structure and function, and ultimately lead to deficits in synaptic plasticity. Our results provide new insight into the role of dominant mutations in subunits of BAF complexes in human intellectual and cognitive disorders.
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, California, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Vogel-Ciernia
authors.forename: Dina P
authors.initials: DP
authors.lastname: Matheos
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Barrett
authors.forename: Enikö A
authors.initials: EA
authors.lastname: Kramár
authors.forename: Soraya
authors.initials: S
authors.lastname: Azzawi
authors.forename: Yuncai
authors.initials: Y
authors.lastname: Chen
authors.forename: Christophe N
authors.initials: CN
authors.lastname: Magnan
authors.forename: Michael
authors.initials: M
authors.lastname: Zeller
authors.forename: Angelina
authors.initials: A
authors.lastname: Sylvain
authors.forename: Jakob
authors.initials: J
authors.lastname: Haettig
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Jia
authors.forename: Anthony
authors.initials: A
authors.lastname: Tran
authors.forename: Richard
authors.initials: R
authors.lastname: Dang
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Post
authors.forename: Meredith
authors.initials: M
authors.lastname: Chabrier
authors.forename: Alex H
authors.initials: AH
authors.lastname: Babayan
authors.forename: Jiang I
authors.initials: JI
authors.lastname: Wu
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Crabtree
authors.forename: Pierre
authors.initials: P
authors.lastname: Baldi
authors.forename: Tallie Z
authors.initials: TZ
authors.lastname: Baram
authors.forename: Gary
authors.initials: G
authors.lastname: Lynch
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Wood
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D049229:Dendritic Spines / Q000502:physiology / Q000648:ultrastructure; D000229:Dependovirus / Q000235:genetics; D000076122:Disks Large Homolog 4 Protein; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005239:Fear / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics*; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D008569:Memory Disorders / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D021641:Recognition, Psychology / Q000502:physiology*; D013997:Time Factors; D059467:Transcriptome
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; C485486:Actl6a protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D051528:Guanylate Kinases