ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
The class 4 semaphorin Sema4D promotes the rapid assembly of GABAergic synapses in rodent hippocampus.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 53 citations in OpenAlex.
- Coordinated Pre- and Postsynaptic Protein Dynamics Underlie Rapid Sema4D-Induced Inhibitory Synapse Assembly.eNeuro · 2026Article
- Coordinated pre- and postsynaptic protein dynamics underlie rapid Sema4D-mediated inhibitory synapse assembly.bioRxiv : the preprint server for biology · 2026Article
- A Multi-omics Exploration Revealing SLIT2 as a Prime Therapeutic Target for Peripheral Facial Paralysis: Integrating Single-Cell Transcriptomics and Plasma Proteome Data.Cellular and molecular neurobiology · 2025Article
- A unifying mechanism for presynaptic homeostatic plasticity at mammalian peripheral and central synapses.Neuron · 2025Article
- Semaphorin heterodimerization in cis regulates membrane targeting and neocortical wiring.Nature communications · 2024Article
- Plexin-B1 and Plexin-B2 play non-redundant roles in GABAergic synapse formation.Molecular and cellular neurosciences · 2024Article
- Cellular and Molecular Mechanisms Underlying Synaptic Subcellular Specificity.Brain sciences · 2024Review
- Semaphorin 4D induced inhibitory synaptogenesis decreases epileptiform activity and alters progression to Status Epilepticus in mice.Epilepsy research · 2023Article
- Plexin-B2 controls the timing of differentiation and the motility of cerebellar granule neurons.eLife · 2021Article
- Modelling and Refining Neuronal Circuits with Guidance Cues: Involvement of Semaphorins.International journal of molecular sciences · 2021Review
- The impact of Semaphorin 4C/Plexin-B2 signaling on fear memory via remodeling of neuronal and synaptic morphology.Molecular psychiatry · 2021Article
- Valproic acid-exposed astrocytes impair inhibitory synapse formation and function.Scientific reports · 2021Article
- Semaphorins in Adult Nervous System Plasticity and Disease.Frontiers in synaptic neuroscience · 2021Review
- LHX6 is essential for the migration of human pluripotent stem cell-derived GABAergic interneurons.Protein & cell · 2020Article
- Semaphorin4D Induces Inhibitory Synapse Formation by Rapid Stabilization of Presynaptic Boutons via MET Coactivation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Class 4 Semaphorins and Plexin-B receptors regulate GABAergic and glutamatergic synapse development in the mammalian hippocampus.Molecular and cellular neurosciences · 2018Article
- The interplay between electrical and chemical synaptogenesis.Journal of neurophysiology · 2018Review
- Semaphorin 4D promotes inhibitory synapse formation and suppresses seizures in vivo.Epilepsia · 2018Article
- Genetic deletion of NMDA receptors suppresses GABAergic synaptic transmission in two distinct types of central neurons.Neuroscience letters · 2018Article
- Transcription and Signaling Regulators in Developing Neuronal Subtypes of Mouse and Human Enteric Nervous System.Gastroenterology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Proper circuit function in the mammalian nervous system depends on the precise assembly and development of excitatory and inhibitory synaptic connections between neurons. Through a loss-of-function genetic screen in cultured hippocampal neurons, we previously identified the class 4 Semaphorin Sema4D as being required for proper GABAergic synapse development. Here we demonstrate that Sema4D is sufficient to promote GABAergic synapse formation in rodent hippocampus and investigate the kinetics of this activity. We find that Sema4D treatment of rat hippocampal neurons increases the density of GABAergic synapses as detected by immunocytochemistry within 30 min, much more rapidly than has been previously described for a prosynaptogenic molecule, and show that this effect is dependent on the Sema4D receptor PlexinB1 using PlxnB1(-/-) mice. Live imaging studies reveal that Sema4D elicits a rapid enhancement (within 10 min) in the rate of addition of synaptic proteins. Therefore, we demonstrate that Sema4D, via PlexinB1, acts to initiate synapse formation by recruiting molecules to both the presynaptic and the postsynaptic terminals; these nascent synapses subsequently become fully functional by 2 h after Sema4D treatment. In addition, acute treatment of an organotypic hippocampal slice epilepsy model with Sema4D reveals that Sema4D rapidly and dramatically alters epileptiform activity, which is consistent with a Sema4D-mediated shift in the balance of excitation and inhibition within the circuit. These data demonstrate an ability to quickly assemble GABAergic synapses in response to an appropriate signal and suggest a potential area of exploration for the development of novel antiepileptic drugs.
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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.