ArticleProceedings of the National Academy of Sciences of the United States of America2014
Connexin hemichannels contribute to spontaneous electrical activity in the human fetal cortex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Changing subplate circuits: Early activity dependent circuit plasticity.Frontiers in cellular neuroscience · 2022Pooled it
- Functional development of midbrain and pons during human gestation and electrophysiological markers for DS intervention.Journal of advanced research · 2026Article
- Subplate neuron dendritic morphology during development in gyrencephalic and lissencephalic brains.Scientific reports · 2026Article
- Diverse roles of connexins in the neuro-vasculature in homeostasis and disease.Translational neuroscience · 2026Review
- Article
- Direct connexin-26 interactions with membrane proteins functionally relevant to the cochlea.Human genetics · 2025Article
- Spontaneous calcium transients in hair cell stereocilia.Scientific reports · 2025Article
- Chronic silencing of Drd1a-Cre+ neurons impairs dopaminergic-driven cortical activation.Frontiers in neuroanatomy · 2025Article
- Development of spontaneous and sensory evoked network activity in rodent cerebral cortexFrontiers in cellular neuroscience · 2025Review
- Electrical Synapses Mediate Embryonic Hyperactivity in a Zebrafish Model of Fragile X Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Human neuronal maturation comes of age: cellular mechanisms and species differences.Nature reviews. Neuroscience · 2024Review
- Connexins in Cancer, the Possible Role of Connexin46 as a Cancer Stem Cell-Determining Protein.Biomolecules · 2023Review
- Geodesic theory of long association fibers arrangement in the human fetal cortex.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- The connexin hemichannel inhibitor D4 produces rapid antidepressant-like effects in mice.Journal of neuroinflammation · 2023Article
- Cortical activity emerges in region-specific patterns during early brain development.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Cortical activity emerges in region-specific patterns during early brain development.bioRxiv : the preprint server for biology · 2023Article
- Axonal connections between S1 barrel, M1, and S2 cortex in the newborn mouse.Frontiers in neuroanatomy · 2023Article
- X-linked Charcot Marie Tooth mutations alter COFrontiers in cellular neuroscience · 2023Article
- Dendritic Spines: Synaptogenesis and Synaptic Pruning for the Developmental Organization of Brain Circuits.Advances in neurobiology · 2023Article
- Connexins and Pannexins: Important Players in Neurodevelopment, Neurological Diseases, and Potential Therapeutics.Biomedicines · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Before the human cortex is able to process sensory information, young postmitotic neurons must maintain occasional bursts of action-potential firing to attract and keep synaptic contacts, to drive gene expression, and to transition to mature membrane properties. Before birth, human subplate (SP) neurons are spontaneously active, displaying bursts of electrical activity (plateau depolarizations with action potentials). Using whole-cell recordings in acute cortical slices, we investigated the source of this early activity. The spontaneous depolarizations in human SP neurons at midgestation (17-23 gestational weeks) were not completely eliminated by tetrodotoxin--a drug that blocks action potential firing and network activity--or by antagonists of glutamatergic, GABAergic, or glycinergic synaptic transmission. We then turned our focus away from standard chemical synapses to connexin-based gap junctions and hemichannels. PCR and immunohistochemical analysis identified the presence of connexins (Cx26/Cx32/Cx36) in the human fetal cortex. However, the connexin-positive cells were not found in clusters but, rather, were dispersed in the SP zone. Also, gap junction-permeable dyes did not diffuse to neighboring cells, suggesting that SP neurons were not strongly coupled to other cells at this age. Application of the gap junction and hemichannel inhibitors octanol, flufenamic acid, and carbenoxolone significantly blocked spontaneous activity. The putative hemichannel antagonist lanthanum alone was a potent inhibitor of the spontaneous activity. Together, these data suggest that connexin hemichannels contribute to spontaneous depolarizations in the human fetal cortex during the second trimester of gestation.
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