Mutation of neuron-specific chromatin remodeling subunit BAF53b: rescue of plasticity and memory by manipulating actin remodeling

Annie Vogel Ciernia; Enikö A Kramár; Dina P Matheos; Robbert Havekes; Thekla J Hemstedt; Christophe N Magnan; Keith Sakata; Ashley Tran; Soraya Azzawi; Alberto Lopez; Richard Dang; Weisheng Wang; Brian Trieu; Joyce Tong; Ruth M Barrett; Rebecca J Post; Pierre Baldi; Ted Abel; Gary Lynch; Marcelo A Wood

doi:10.1101/lm.044602.116

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Mutation of neuron-specific chromatin remodeling subunit BAF53b: rescue of plasticity and memory by manipulating actin remodeling

Journal article

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Mutation of neuron-specific chromatin remodeling subunit BAF53b: rescue of plasticity and memory by manipulating actin remodeling

Annie Vogel Ciernia, Enikö A Kramár, Dina P Matheos, Robbert Havekes, Thekla J Hemstedt, Christophe N Magnan, Keith Sakata, Ashley Tran, Soraya Azzawi, Alberto Lopez, …

Learning & memory (Cold Spring Harbor, N.Y.), Vol.24(5), pp.199-209

05/2017

DOI: 10.1101/lm.044602.116

PMCID: PMC5397687

PMID: 28416631

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Abstract

Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons. We generated transgenic mice lacking subdomain 2 of Baf53b (BAF53bΔSB2). Long-term synaptic potentiation (LTP) and long-term memory, both of which are associated with phosphorylation of the actin severing protein cofilin, were assessed in these animals. A phosphorylation mimic of cofilin was stereotaxically delivered into the hippocampus of BAF53bΔSB2 mice in an effort to rescue LTP and memory. BAF53bΔSB2 mutant mice show impairments in phosphorylation of synaptic cofilin, LTP, and memory. Both the synaptic plasticity and memory deficits are rescued by overexpression of a phosphorylation mimetic of cofilin. Baseline physiology and behavior were not affected by the mutation or the experimental treatment. This study suggests a potential link between nBAF function, actin cytoskeletal remodeling at the dendritic spine, and memory formation. This work shows that a targeted manipulation of synaptic function can rescue adult plasticity and memory deficits caused by manipulations of nBAF, and thereby provides potential novel avenues for therapeutic development for multiple intellectual disability disorders.

Actin Depolymerizing Factors - genetics

Chromatin Assembly and Disassembly - genetics

Phosphopyruvate Hydratase - metabolism

Nerve Net - physiology

Actin Depolymerizing Factors - metabolism

Neuronal Plasticity - genetics

Phosphorylation - genetics

Neurons - ultrastructure

Phosphopyruvate Hydratase - genetics

Cell Nucleolus - metabolism

Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism

Transduction, Genetic

Chromosomal Proteins, Non-Histone - metabolism

Mice, Inbred C57BL

Mice, Transgenic

Long-Term Potentiation - genetics

Hippocampus - cytology

Mutation - genetics

Chromosomal Proteins, Non-Histone - genetics

Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics

Hippocampus - metabolism

Animals

Mice

In Vitro Techniques

Memory - physiology

Sequence Deletion - genetics

Details

Title: Subtitle: Mutation of neuron-specific chromatin remodeling subunit BAF53b: rescue of plasticity and memory by manipulating actin remodeling
Creators: Annie Vogel Ciernia - Department of Medical Microbiology and Immunology, University of California, Davis, California 95656, USA
Enikö A Kramár - Center for the Neurobiology of Learning and Memory, Irvine, California, USA
Dina P Matheos - Center for the Neurobiology of Learning and Memory, Irvine, California, USA
Robbert Havekes - Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen 9712, The Netherlands
Thekla J Hemstedt - Center for the Neurobiology of Learning and Memory, Irvine, California, USA
Christophe N Magnan - Institute for Genomics and Bioinformatics, University of California, Irvine, California 92697, USA
Keith Sakata - Center for the Neurobiology of Learning and Memory, Irvine, California, USA
Ashley Tran - Center for the Neurobiology of Learning and Memory, Irvine, California, USA
Soraya Azzawi - Center for the Neurobiology of Learning and Memory, Irvine, California, USA
Alberto Lopez - Center for the Neurobiology of Learning and Memory, Irvine, California, USA
Richard Dang - Center for the Neurobiology of Learning and Memory, Irvine, California, USA
Weisheng Wang - Institute for Genomics and Bioinformatics, University of California, Irvine, California 92697, USA
Brian Trieu - Department of Psychiatry and Human Behavior, University of California, Irvine, California 92697, USA
Joyce Tong - Center for the Neurobiology of Learning and Memory, Irvine, California, USA
Ruth M Barrett - Oregon Health and Science University, Portland, Oregon 97239, USA
Rebecca J Post - Center for the Neurobiology of Learning and Memory, Irvine, California, USA
Pierre Baldi - Institute for Genomics and Bioinformatics, University of California, Irvine, California 92697, USA
Ted Abel - Departments of Molecular Physiology and Biophysics, Psychiatry, and Biochemistry, Iowa Neuroscience Institute, Iowa City, Iowa 50309, USA
Gary Lynch - Department of Psychiatry and Human Behavior, University of California, Irvine, California 92697, USA
Marcelo A Wood - Institute for Genomics and Bioinformatics, University of California, Irvine, California 92697, USA
Resource Type: Journal article
Publication Details: Learning & memory (Cold Spring Harbor, N.Y.), Vol.24(5), pp.199-209
DOI: 10.1101/lm.044602.116
PMID: 28416631
PMCID: PMC5397687
NLM abbreviation: Learn Mem
ISSN: 1072-0502
eISSN: 1549-5485
Publisher: United States
Grant note: R01 DA036984 / NIDA NIH HHS R01 MH101491 / NIMH NIH HHS R01 MH087463 / NIMH NIH HHS
Language: English
Date published: 05/2017
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065838802771

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