TY - JOUR T1 - Circuit-Specific Intracortical Hyperconnectivity in Mice with Deletion of the Autism-Associated <em>Met</em> Receptor Tyrosine Kinase JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5855 LP - 5864 DO - 10.1523/JNEUROSCI.6569-10.2011 VL - 31 IS - 15 AU - Shenfeng Qiu AU - Charles T. Anderson AU - Pat Levitt AU - Gordon M. G. Shepherd Y1 - 2011/04/13 UR - http://www.jneurosci.org/content/31/15/5855.abstract N2 - 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. ER -