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- Title
Circuit-Specific Intracortical Hyperconnectivity in Mice with Deletion of the Autism-Associated Met Receptor Tyrosine Kinase.
- Authors
Shenfeng Qiu; Anderson, Charles T.; Levitt, Pat; Shepherd, Gordon M. G.
- 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.
- Subjects
MET receptor; AUTISM spectrum disorders; PROTEIN-tyrosine kinases; NEOCORTEX; GLUTAMIC acid; GENETIC carriers; LABORATORY mice
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 15, p5855
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.6569-10.2011