ArticleCerebral cortex (New York, N.Y. : 1991)2015
Asynchronous GABA Release Is a Key Determinant of Tonic Inhibition and Controls Neuronal Excitability: A Study in the Synapsin II-/- Mouse.
Article in Cerebral cortex (New York, N.Y. : 1991), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- Social regression stems from a latent phase of GABAergic dysfunction and sensory breakdown in a model of synaptopathy.Molecular psychiatry · 2026Article
- Impact of distinct neurotransmitter release modes on neuronal signaling.Molecular psychiatry · 2026Review
- Presynaptic maturation of inhibitory connections onto vasoactive intestinal polypeptide-expressing GABAergic interneurons in the mouse barrel field.Pflugers Archiv : European journal of physiology · 2025Article
- The Lack of Synapsin Alters Presynaptic Plasticity at Hippocampal Mossy Fibers in Male Mice.eNeuro · 2024Article
- Increased presynaptic excitability in a migraine with aura mutation.Brain : a journal of neurology · 2024Article
- Early endocannabinoid-mediated depolarization-induced suppression of excitation delays the appearance of the epileptic phenotype in synapsin II knockout mice.Cellular and molecular life sciences : CMLS · 2024Article
- Low glycemic index diet restrains epileptogenesis in a gender-specific fashion.Cellular and molecular life sciences : CMLS · 2023Article
- Two forms of asynchronous release with distinctive spatiotemporal dynamics in central synapses.eLife · 2023Article
- Synapsin II Directly Suppresses Epileptic Seizures In Vivo.Brain sciences · 2022Article
- Xenon LFP Analysis Platform Is a Novel Graphical User Interface for Analysis of Local Field Potential From Large-Scale MEA Recordings.Frontiers in neuroscience · 2022Article
- A familiar study on self-limited childhood epilepsy patients using hIPSC-derived neurons shows a bias towards immaturity at the morphological, electrophysiological and gene expression levels.Stem cell research & therapy · 2021Article
- Recent advances in gene therapy for neurodevelopmental disorders with epilepsy.Journal of neurochemistry · 2021Review
- Physical Activity Reduces Epilepsy Incidence: a Retrospective Cohort Study in Swedish Cross-Country Skiers and an Experimental Study in Seizure-Prone Synapsin II Knockout Mice.Sports medicine - open · 2019Article
- Growth and excitability at synapsin II deficient hippocampal neurons.Molecular and cellular neurosciences · 2019Article
- Technologies to Study Action Potential Propagation With a Focus on HD-MEAs.Frontiers in cellular neuroscience · 2019Article
- Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model.Frontiers in pharmacology · 2019Article
- Synapsin I and Synapsin II regulate neurogenesis in the dentate gyrus of adult mice.Oncotarget · 2018Article
- Inhibitory or excitatory? Optogenetic interrogation of the functional roles of GABAergic interneurons in epileptogenesis.Journal of biomedical science · 2017Review
- Impaired GABAOncotarget · 2017Article
- Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets.Pharmacological reviews · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Idiopathic epilepsies have frequently been linked to mutations in voltage-gated channels (channelopathies); recently, mutations in several genes encoding presynaptic proteins have been shown to cause epilepsy in humans and mice, indicating that epilepsy can also be considered a synaptopathy. However, the functional mechanisms by which presynaptic dysfunctions lead to hyperexcitability and seizures are not well understood. We show that deletion of synapsin II (Syn II), a presynaptic protein contributing to epilepsy predisposition in humans, leads to a loss of tonic inhibition in mouse hippocampal slices due to a dramatic decrease in presynaptic asynchronous GABA release. We also show that the asynchronous GABA release reduces postsynaptic cell firing, and the parallel impairment of asynchronous GABA release and tonic inhibition results in an increased excitability at both single-neuron and network levels. Restoring tonic inhibition with THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; gaboxadol), a selective agonist of δ subunit-containing GABAA receptors, fully rescues the SynII(-/-) epileptic phenotype both ex vivo and in vivo. The results demonstrate a causal relationship between the dynamics of GABA release and the generation of tonic inhibition, and identify a novel mechanism of epileptogenesis generated by dysfunctions in the dynamics of release that can be effectively targeted by novel antiepileptic strategies.
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Registered trials
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.