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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Tring, Elaine Golshani, Peyman Trachtenberg, Joshua T. Garcia-junco-clemente, Pablo Chow, David K. Lazaro, Maria T. |
| Description | Author Affiliation: Garcia-Junco-Clemente P ( Departments of Neurobiology and Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095.); |
| Abstract | De novo phosphatase and tensin homolog on chromosome ten (PTEN) mutations are a cause of sporadic autism. How single-copy loss of PTEN alters neural function is not understood. Here we report that Pten haploinsufficiency increases the expression of small-conductance calcium-activated potassium channels. The resultant augmentation of this conductance increases the amplitude of the afterspike hyperpolarization, causing a decrease in intrinsic excitability. In vivo, this change in intrinsic excitability reduces evoked firing rates of cortical pyramidal neurons but does not alter receptive field tuning. The decreased in vivo firing rate is not associated with deficits in the dendritic integration of synaptic input or with changes in dendritic complexity. These findings identify calcium-activated potassium channelopathy as a cause of cortical dysfunction in the PTEN model of autism and provide potential molecular therapeutic targets. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 45 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Autistic Disorder Genetics Channelopathies Physiopathology PTEN Phosphohydrolase Small-Conductance Calcium-Activated Potassium Channels Metabolism Analysis Of Variance Animals Blotting, Western Hemizygote Mice Mutation Patch-Clamp Techniques Pyramidal Tracts Cytology Physiology Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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