ArticleProceedings of the National Academy of Sciences of the United States of America2015
Activity-dependent inhibitory synapse remodeling through gephyrin phosphorylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 115 citations in OpenAlex.
- ICER-Controlled inhibitory plasticity of amygdala engram neurons regulates fear memory precision.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Neuroligin-2-Dependent Adhesion Defines a Molecular Checkpoint for Inhibitory Synaptic Plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Cryo-EM structures of higher order Gephyrin oligomers reveal principles of inhibitory postsynaptic scaffold organization.Nature communications · 2026Article
- Redox-Activated Probes Enable High-Contrast Live Imaging of Native Postsynaptic Scaffolds.Angewandte Chemie (International ed. in English) · 2026Article
- One-step induction of human GABAergic neurons promotes presynaptic development & synapse maturation.bioRxiv : the preprint server for biology · 2025Article
- Is the Activation of the Postsynaptic Ligand Gated Glycine- or GABABiomedicines · 2025Review
- Activity-dependent development of synaptic circuits mediates direction selectivity in an axis-specific manner.Cell reports · 2025Article
- Release your inhibitions: The cell biology of GABAergic postsynaptic plasticity.Current opinion in neurobiology · 2025Review
- Chronic benzodiazepine treatment triggers gephyrin scaffold destabilization and GABAFrontiers in cellular neuroscience · 2025Article
- Neurobeachin regulates receptor downscaling at GABAergic inhibitory synapses in a protein kinase A-dependent manner.Communications biology · 2024Article
- Learning-induced remodelling of inhibitory synapses in the motor cortex.Open biology · 2024Article
- Ultrastructural characterization of hippocampal inhibitory synapses under resting and stimulated conditions.Molecular brain · 2024Article
- Distinct Thalamo-Subcortical Circuits Underlie Painful Behavior and Depression-Like Behavior Following Nerve Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Gephyrin phosphorylation facilitates sexually dimorphic development and function of parvalbumin interneurons in the mouse hippocampus.Molecular psychiatry · 2024Article
- Thermodynamic modulation of gephyrin condensation by inhibitory synapse components.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The gephyrin scaffold modulates cortical layer 2/3 pyramidal neuron responsiveness to single whisker stimulation.Scientific reports · 2024Article
- Amyloid Pathology Impairs Experience-Dependent Inhibitory Synaptic Plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Dissection of signaling pathways regulating TrkB-dependent gephyrin clustering.Frontiers in molecular neuroscience · 2024Article
- Amyloid pathology impairs experience-dependent inhibitory synaptic plasticity.bioRxiv : the preprint server for biology · 2023Article
- UNC-43/CaMKII-triggered anterograde signals recruit GABANature communications · 2023Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Maintaining a proper balance between excitation and inhibition is essential for the functioning of neuronal networks. However, little is known about the mechanisms through which excitatory activity can affect inhibitory synapse plasticity. Here we used tagged gephyrin, one of the main scaffolding proteins of the postsynaptic density at GABAergic synapses, to monitor the activity-dependent adaptation of perisomatic inhibitory synapses over prolonged periods of time in hippocampal slice cultures. We find that learning-related activity patterns known to induce N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation and transient optogenetic activation of single neurons induce within hours a robust increase in the formation and size of gephyrin-tagged clusters at inhibitory synapses identified by correlated confocal electron microscopy. This inhibitory morphological plasticity was associated with an increase in spontaneous inhibitory activity but did not require activation of GABAA receptors. Importantly, this activity-dependent inhibitory plasticity was prevented by pharmacological blockade of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), it was associated with an increased phosphorylation of gephyrin on a site targeted by CaMKII, and could be prevented or mimicked by gephyrin phospho-mutants for this site. These results reveal a homeostatic mechanism through which activity regulates the dynamics and function of perisomatic inhibitory synapses, and they identify a CaMKII-dependent phosphorylation site on gephyrin as critically important for this process.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.