scholarly journals Crh and Oprm1 mediate anxiety-related behavior and social approach in a mouse model of MECP2 duplication syndrome

2012 ◽  
Vol 44 (2) ◽  
pp. 206-211 ◽  
Author(s):  
Rodney C Samaco ◽  
Caleigh Mandel-Brehm ◽  
Christopher M McGraw ◽  
Chad A Shaw ◽  
Bryan E McGill ◽  
...  
Keyword(s):  
Mouse Model ◽  
Social Approach ◽  
Mecp2 Duplication Syndrome ◽  
Duplication Syndrome

scholarly journals Increased Axonal Bouton Stability during Learning in the Mouse Model of MECP2 Duplication Syndrome

eNeuro ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. ENEURO.0056-17.2018 ◽  
Author(s):  
Ryan T. Ash ◽  
Paul G. Fahey ◽  
Jiyoung Park ◽  
Huda Y. Zoghbi ◽  
Stelios M. Smirnakis
Keyword(s):  
Mouse Model ◽  
Mecp2 Duplication Syndrome ◽  
Duplication Syndrome

scholarly journals Altered visual cortical processing in a mouse model of MECP2 duplication syndrome

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Dinghong Zhang ◽  
Bin Yu ◽  
Jing Liu ◽  
Weiqian Jiang ◽  
Taorong Xie ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cortical Processing ◽  
Mecp2 Duplication Syndrome ◽  
Visual Cortical ◽  
Duplication Syndrome

scholarly journals Excessive ERK-dependent synaptic clustering drives enhanced motor learning in the MECP2 duplication syndrome mouse model of autism

2017 ◽  
Author(s):  
Ryan Thomas Ash ◽  
Shelly Alexandra Buffington ◽  
Jiyoung Park ◽  
Mauro Costa-Mattioli ◽  
Huda Yaya Zoghbi ◽  
...  
Keyword(s):  
Motor Learning ◽  
Mouse Model ◽  
Learning And Memory ◽  
Erk Signaling ◽  
Learning Abilities ◽  
Spine Stabilization ◽  
Syndromic Autism ◽  
Mecp2 Duplication Syndrome ◽  
Repetitive Motor ◽  
Duplication Syndrome

AbstractAutism-associated genetic mutations may produce altered learning abilities by perturbing the balance between stability and plasticity of synaptic connections in the brain. Here we report an increase in the stabilization of dendritic spines formed during repetitive motor learning in the mouse model of MECP2-duplication syndrome, a high-penetrance form of syndromic autism. This increased stabilization is mediated entirely by spines that form cooperatively in clusters. The number of clusters formed and stabilized predicts the mutant’s enhanced motor learning and memory phenotype, reminiscent of savant-like behaviors occasionally associated with autism.The ERK signaling pathway, which promotes cooperative plasticity between spines, was found to be hyperactive in MECP2-duplication motor cortex specifically after training. Inhibition of ERK signaling normalizes clustered spine stabilization and rescues motor learning behavior in mutants. We conclude that learning-associated dendritic spine clustering stabilized by hyperactive ERK signaling drives abnormal motor learning and memory consolidation in this model of syndromic autism.

scholarly journals Genetic Reduction or Negative Modulation of mGlu7 Does Not Impact Anxiety and Fear Learning Phenotypes in a Mouse Model of MECP2 Duplication Syndrome

2017 ◽  
Vol 9 (9) ◽  
pp. 2210-2217 ◽  
Author(s):  
Nicole M. Fisher ◽  
Rocco G. Gogliotti ◽  
Sheryl Anne D. Vermudez ◽  
Branden J. Stansley ◽  
P. Jeffrey Conn ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fear Learning ◽  
Mecp2 Duplication Syndrome ◽  
Anxiety And Fear ◽  
Duplication Syndrome

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

2017 ◽  
Author(s):  
Ryan T. Ash ◽  
Paul G. Fahey ◽  
Jiyoung Park ◽  
Huda Y. Zoghbi ◽  
Stelios M. Smirnakis
Keyword(s):  
Motor Learning ◽  
Mouse Model ◽  
Dendritic Spine ◽  
Pyramidal Neuron ◽  
Structural Plasticity ◽  
Autism Spectrum ◽  
Wild Type ◽  
Syndromic Autism ◽  
Mecp2 Duplication Syndrome ◽  
Duplication Syndrome

ABSTRACTMECP2-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 STATEMENTAbnormal 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.

scholarly journals Dendritic Arborization and Spine Dynamics Are Abnormal in the Mouse Model of MECP2 Duplication Syndrome

2013 ◽  
Vol 33 (50) ◽  
pp. 19518-19533 ◽  
Author(s):  
M. Jiang ◽  
R. T. Ash ◽  
S. A. Baker ◽  
B. Suter ◽  
A. Ferguson ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dendritic Arborization ◽  
Mecp2 Duplication Syndrome ◽  
Spine Dynamics ◽  
Duplication Syndrome

scholarly journals A Mouse Model for MeCP2 Duplication Syndrome: MeCP2 Overexpression Impairs Learning and Memory and Synaptic Transmission

2012 ◽  
Vol 32 (9) ◽  
pp. 3109-3117 ◽  
Author(s):  
E. S. Na ◽  
E. D. Nelson ◽  
M. Adachi ◽  
A. E. Autry ◽  
M. A. Mahgoub ◽  
...  
Keyword(s):  
Mouse Model ◽  
Synaptic Transmission ◽  
Learning And Memory ◽  
Mecp2 Duplication Syndrome ◽  
Duplication Syndrome
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