title: Overexpression of calcium-activated potassium channels underlies cortical dysfunction in a model of PTEN-associated autism.
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.
authors.affiliation: Departments of Neurobiology and Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095.
authors.forename: Pablo
authors.initials: P
authors.lastname: Garcia-Junco-Clemente
authors.forename: David K
authors.initials: DK
authors.lastname: Chow
authors.forename: Elaine
authors.initials: E
authors.lastname: Tring
authors.forename: Maria T
authors.initials: MT
authors.lastname: Lazaro
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Trachtenberg
authors.forename: Peyman
authors.initials: P
authors.lastname: Golshani
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000503:physiopathology; D015153:Blotting, Western; D053447:Channelopathies / Q000235:genetics / Q000503:physiopathology*; D057898:Hemizygote; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D018408:Patch-Clamp Techniques; D011712:Pyramidal Tracts / Q000166:cytology / Q000502:physiology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D051640:Small-Conductance Calcium-Activated Potassium Channels; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: SK; gain; mTOR; sensory processing; visual cortex