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Articles, Neurobiology of Disease

Circuit-Specific Intracortical Hyperconnectivity in Mice with Deletion of the Autism-Associated Met Receptor Tyrosine Kinase

Shenfeng Qiu, Charles T. Anderson, Pat Levitt and Gordon M. G. Shepherd
Journal of Neuroscience 13 April 2011, 31 (15) 5855-5864; DOI: https://doi.org/10.1523/JNEUROSCI.6569-10.2011
Shenfeng Qiu
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Charles T. Anderson
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Pat Levitt
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Gordon M. G. Shepherd
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Abstract

Local hyperconnectivity in the neocortex is a hypothesized pathophysiological state in autism spectrum disorder (ASD). MET, a receptor tyrosine kinase that regulates dendrite and spine morphogenesis, has been established as a risk gene for ASD. Here, we analyzed the synaptic circuit organization of identified pyramidal neurons in the anterior frontal cortex of mice with a dorsal pallium-derived, conditional knock-out (cKO) of Met. Synaptic mapping by glutamate uncaging identified layer 2/3 as the main source of local excitatory input to layer 5 projection neurons in controls. In both cKO and heterozygotes, this pathway was stronger by a factor of ∼2. This increase was both sublayer and projection-class specific, restricted to corticostriatal neurons in upper layer 5B and not neighboring corticopontine neurons. Paired recordings in cKO slices demonstrated increased unitary connectivity. We propose that excitatory hyperconnectivity in specific neocortical microcircuits constitutes a physiological basis for Met-mediated ASD risk.

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The Journal of Neuroscience: 31 (15)
Journal of Neuroscience
Vol. 31, Issue 15
13 Apr 2011
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Circuit-Specific Intracortical Hyperconnectivity in Mice with Deletion of the Autism-Associated Met Receptor Tyrosine Kinase
Shenfeng Qiu, Charles T. Anderson, Pat Levitt, Gordon M. G. Shepherd
Journal of Neuroscience 13 April 2011, 31 (15) 5855-5864; DOI: 10.1523/JNEUROSCI.6569-10.2011

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Circuit-Specific Intracortical Hyperconnectivity in Mice with Deletion of the Autism-Associated Met Receptor Tyrosine Kinase
Shenfeng Qiu, Charles T. Anderson, Pat Levitt, Gordon M. G. Shepherd
Journal of Neuroscience 13 April 2011, 31 (15) 5855-5864; DOI: 10.1523/JNEUROSCI.6569-10.2011
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