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Increased axonal bouton stability during learning in the mouse model of MECP2 duplication syndrome

Ryan T. Ash, Paul G. Fahey, Jiyoung Park, Huda Y. Zoghbi, Stelios M. Smirnakis
doi: https://doi.org/10.1101/186239
Ryan T. Ash
1Department of Neurology, Brigham and Women’s Hospital and Jamaica Plain Veterans Administration Hospital, Harvard Medical School, Boston, MA 02115
2Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030
3Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030
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Paul G. Fahey
2Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030
3Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030
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Jiyoung Park
3Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030
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Huda Y. Zoghbi
3Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030
4Department of Pediatrics, Texas Children’s Hospital and Baylor College of Medicine, Houston, TX 77030
5Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 USA
6Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, United States
7Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030
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Stelios M. Smirnakis
1Department of Neurology, Brigham and Women’s Hospital and Jamaica Plain Veterans Administration Hospital, Harvard Medical School, Boston, MA 02115
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  • For correspondence: SMSMIRNAKIS@partners.org
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ABSTRACT

MECP2-duplication syndrome is an X-linked form of syndromic autism caused by genomic duplication of the region encoding Methyl-CpG-binding protein 2. Mice overexpressing MECP2 demonstrate altered patterns of learning and memory, including enhanced motor learning. Previous work associated this enhanced motor learning to abnormally increased stability of dendritic spine clusters formed in the apical tuft of corticospinal, area M1, neurons during rotarod training. In the current study, we measure the structural plasticity of axonal boutons in Layer 5 (L5) pyramidal neuron projections to layer 1 of area M1 during motor learning. In wild-type mice we find that during rotarod training, bouton formation rate changes minimally, if at all, while bouton elimination rate doubles. Notably, the observed upregulation in bouton elimination with learning is absent in MECP2-duplication mice. This result provides further evidence of imbalance between structural stability and plasticity in this form of syndromic autism. Furthermore, the observation that axonal bouton elimination doubles with motor learning in wild-type animals contrasts with the increase of dendritic spine consolidation observed in corticospinal neurons at the same layer. This dissociation suggests that different area M1 microcircuits may manifest different patterns of structural synaptic plasticity during motor learning.

SIGNIFICANCE STATEMENT Abnormal balance between synaptic stability and plasticity is a feature of several autism spectrum disorders, often corroborated by in vivo studies of dendritic spine turnover. Here we provide the first evidence that abnormally increased stability of axonal boutons, the presynaptic component of excitatory synapses, occurs during motor learning in the MECP2 duplication syndrome mouse model of autism. In contrast, in normal controls, axonal bouton elimination in L5 pyramidal neuron projections to layer 1 of area M1 doubles with motor learning. The fact that axonal projection boutons get eliminated, while corticospinal dendritic spines get consolidated with motor learning in layer 1 of area M1, suggests that structural plasticity manifestations differ across different M1 microcircuits.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 08, 2017.
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Increased axonal bouton stability during learning in the mouse model of MECP2 duplication syndrome
Ryan T. Ash, Paul G. Fahey, Jiyoung Park, Huda Y. Zoghbi, Stelios M. Smirnakis
bioRxiv 186239; doi: https://doi.org/10.1101/186239
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Increased axonal bouton stability during learning in the mouse model of MECP2 duplication syndrome
Ryan T. Ash, Paul G. Fahey, Jiyoung Park, Huda Y. Zoghbi, Stelios M. Smirnakis
bioRxiv 186239; doi: https://doi.org/10.1101/186239

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