Autism-Associated Shank3 Is Essential for Homeostatic Compensation in Rodent V1
| Autor: | Nathaniel J. Miska, Vedakumar Tatavarty, Stephen D. Van Hooser, Keith B. Hengen, Heather Lin, Alejandro Torrado Pacheco, Gina G. Turrigiano, Priya Koundinya, Chelsea Groves Kuhnle, Florence F. Wagner |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Nerve Tissue Proteins Sensory system Tetrodotoxin Biology Article Glycogen Synthase Kinase 3 Mice 03 medical and health sciences 0302 clinical medicine Antimanic Agents Homeostatic plasticity Neural Pathways medicine Animals Homeostasis Autistic Disorder Visual Cortex Mice Knockout Neurons Neuronal Plasticity Synaptic scaling Behavior Animal General Neuroscience Microfilament Proteins Excitatory Postsynaptic Potentials medicine.disease Grooming Phenotype Rats 030104 developmental biology Visual cortex medicine.anatomical_structure Gene Knockdown Techniques Knockout mouse Lithium Compounds Autism Neuroscience 030217 neurology & neurosurgery Sodium Channel Blockers |
| Zdroj: | Neuron |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2020.02.033 |
| Popis: | Summary Mutations in Shank3 are strongly associated with autism spectrum disorders and neural circuit changes in several brain areas, but the cellular mechanisms that underlie these defects are not understood. Homeostatic forms of plasticity allow central circuits to maintain stable function during experience-dependent development, leading us to ask whether loss of Shank3 might impair homeostatic plasticity and circuit-level compensation to perturbations. We found that Shank3 loss in vitro abolished synaptic scaling and intrinsic homeostatic plasticity, deficits that could be rescued by treatment with lithium. Further, Shank3 knockout severely compromised the in vivo ability of visual cortical circuits to recover from perturbations to sensory drive. Finally, lithium treatment ameliorated a repetitive self-grooming phenotype in Shank3 knockout mice. These findings demonstrate that Shank3 loss severely impairs the ability of central circuits to harness homeostatic mechanisms to compensate for perturbations in drive, which, in turn, may render them more vulnerable to such perturbations. |
| Databáze: | OpenAIRE |
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