Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism
- PMID: 22983708
- DOI: 10.1126/science.1224159
Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism
Abstract
The genetic heterogeneity of autism poses a major challenge for identifying mechanism-based treatments. A number of rare mutations are associated with autism, and it is unclear whether these result in common neuronal alterations. Monogenic syndromes, such as fragile X, include autism as one of their multifaceted symptoms and have revealed specific defects in synaptic plasticity. We discovered an unexpected convergence of synaptic pathophysiology in a nonsyndromic form of autism with those in fragile X syndrome. Neuroligin-3 knockout mice (a model for nonsyndromic autism) exhibited disrupted heterosynaptic competition and perturbed metabotropic glutamate receptor-dependent synaptic plasticity, a hallmark of fragile X. These phenotypes could be rescued by reexpression of neuroligin-3 in juvenile mice, highlighting the possibility of reverting neuronal circuit alterations in autism after the completion of development.
Similar articles
-
[Abnormalities of synaptogenesis in autism. Pathogenic and therapeutic implications].Rev Neurol. 2012 Feb 29;54 Suppl 1:S41-50. Rev Neurol. 2012. PMID: 22374772 Review. Spanish.
-
Altered synaptic plasticity in a mouse model of fragile X mental retardation.Proc Natl Acad Sci U S A. 2002 May 28;99(11):7746-50. doi: 10.1073/pnas.122205699. Proc Natl Acad Sci U S A. 2002. PMID: 12032354 Free PMC article.
-
Developmental plasticity shapes synaptic phenotypes of autism-associated neuroligin-3 mutations in the calyx of Held.Mol Psychiatry. 2017 Oct;22(10):1483-1491. doi: 10.1038/mp.2016.157. Epub 2016 Oct 11. Mol Psychiatry. 2017. PMID: 27725662 Free PMC article.
-
Heterogeneity and convergence: the synaptic pathophysiology of autism.Eur J Neurosci. 2014 Apr;39(7):1107-13. doi: 10.1111/ejn.12498. Eur J Neurosci. 2014. PMID: 24712990 Review.
-
[Synapse maturation and autism: learning from neuroligin model mice].Nihon Shinkei Seishin Yakurigaku Zasshi. 2014 Feb;34(1):1-4. Nihon Shinkei Seishin Yakurigaku Zasshi. 2014. PMID: 25069265 Review. Japanese.
Cited by
-
Sushi domain-containing protein 4 controls synaptic plasticity and motor learning.Elife. 2021 Mar 4;10:e65712. doi: 10.7554/eLife.65712. Elife. 2021. PMID: 33661101 Free PMC article.
-
Region-Specific Phosphorylation Determines Neuroligin-3 Localization to Excitatory Versus Inhibitory Synapses.Biol Psychiatry. 2024 Nov 15;96(10):815-828. doi: 10.1016/j.biopsych.2023.12.020. Epub 2023 Dec 27. Biol Psychiatry. 2024. PMID: 38154503
-
Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics.Curr Top Behav Neurosci. 2016;28:1-52. doi: 10.1007/7854_2015_5003. Curr Top Behav Neurosci. 2016. PMID: 27305922 Free PMC article. Review.
-
Hyperexcitability and Hyperplasticity Disrupt Cerebellar Signal Transfer in the IB2 KO Mouse Model of Autism.J Neurosci. 2019 Mar 27;39(13):2383-2397. doi: 10.1523/JNEUROSCI.1985-18.2019. Epub 2019 Jan 29. J Neurosci. 2019. PMID: 30696733 Free PMC article.
-
Heterogeneity of Cell Surface Glutamate and GABA Receptor Expression in Shank and CNTN4 Autism Mouse Models.Front Mol Neurosci. 2018 Jun 19;11:212. doi: 10.3389/fnmol.2018.00212. eCollection 2018. Front Mol Neurosci. 2018. PMID: 29970989 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
