ArticleMolecular psychiatry2021
Inhibitory regulation of calcium transients in prefrontal dendritic spines is compromised by a nonsense Shank3 mutation.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Linear ubiquitination of the NMDA receptor GluN2A subunit facilitates the GluN2B-to-GluN2A switch and synaptic maturation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Autism-associatedProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Early postnatal dysfunction of ACC PV interneurons in Shank3BMolecular psychiatry · 2025Article
- Male caregiving experience alters hippocampal neuroplasticity and transcription independent of reproduction in a biparental species.Communications biology · 2025Article
- Comprehensive behavioral characterization and impaired hippocampal synaptic transmission in R1117X Shank3 mutant mice.Translational psychiatry · 2025Article
- Scn2a-linked myelination deficits and synaptic plasticity alterations drive auditory processing disorders in an ASD mouse model.Nature communications · 2025Article
- Impaired Spatiotemporal Encoding of Social Behavior and Anxiety in the Prefrontal Cortex of Mice Lacking ASD-Risk GenebioRxiv : the preprint server for biology · 2025Article
- Article
- Structural neural plasticity evoked by rapid-acting antidepressant interventions.Nature reviews. Neuroscience · 2025Review
- Rare genetic brain disorders with overlapping neurological and psychiatric phenotypes.Nature reviews. Neurology · 2024Review
- The NO Answer for Autism Spectrum Disorder.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- YBX1-Mediated DNA Methylation-Dependent SHANK3 Expression in PBMCs and Developing Cortical Interneurons in Schizophrenia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Shank3 related muscular hypotonia is accompanied by increased intracellular calcium concentrations and ion channel dysregulation in striated muscle tissue.Frontiers in cell and developmental biology · 2023Article
- Prefrontal Interneurons: Populations, Pathways, and Plasticity Supporting Typical and Disordered Cognition in Rodent Models.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Review
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo.Neuron · 2021Article
- Eavesdropping wires: Recording activity in axons using genetically encoded calcium indicators.Journal of neuroscience methods · 2021Review
- A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics.Trends in neurosciences · 2021Review
- Secondary motor cortex: Broadcasting and biasing animal's decisions through long-range circuits.International review of neurobiology · 2021Review
- Cumulative Effects of Social Stress on Reward-Guided Actions and Prefrontal Cortical Activity.Biological psychiatry · 2020Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The SHANK3 gene encodes a postsynaptic scaffold protein in excitatory synapses, and its disruption is implicated in neurodevelopmental disorders such as Phelan-McDermid syndrome, autism spectrum disorder, and schizophrenia. Most studies of SHANK3 in the neocortex and hippocampus have focused on disturbances in pyramidal neurons. However, GABAergic interneurons likewise receive excitatory inputs and presumably would also be a target of constitutive SHANK3 perturbations. In this study, we characterize the prefrontal cortical microcircuit in awake mice using subcellular-resolution two-photon microscopy. We focused on a nonsense R1117X mutation, which leads to truncated SHANK3 and has been linked previously to cortical dysfunction. We find that R1117X mutants have abnormally elevated calcium transients in apical dendritic spines. The synaptic calcium dysregulation is due to a loss of dendritic inhibition via decreased NMDAR currents and reduced firing of dendrite-targeting somatostatin-expressing (SST) GABAergic interneurons. Notably, upregulation of the NMDAR subunit GluN2B in SST interneurons corrects the excessive synaptic calcium signals and ameliorates learning deficits in R1117X mutants. These findings reveal dendrite-targeting interneurons, and more broadly the inhibitory control of dendritic spines, as a key microcircuit mechanism compromised by the SHANK3 dysfunction.
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