ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Heterotopic neurons with altered inhibitory synaptic function in an animal model of malformation-associated epilepsy.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 59 citations in OpenAlex.
- Human periventricular nodular heterotopia shows several interictal epileptic patterns and hyperexcitability of neuronal firing.Frontiers in neurology · 2022Article
- Prenatal Hypoxia-Ischemia Induces Abnormalities in CA3 Microstructure, Potassium Chloride Co-Transporter 2 Expression and Inhibitory Tone.Frontiers in cellular neuroscience · 2015Article
- Altered migratory behavior of interneurons in a model of cortical dysplasia: the influence of elevated GABAA activity.Cerebral cortex (New York, N.Y. : 1991) · 2014Article
- Targeted disruption of layer 4 during development increases GABAA receptor neurotransmission in the neocortex.Journal of neurophysiology · 2014Article
- Glial glutamate transporter and glutamine synthetase regulate GABAergic synaptic strength in the spinal dorsal horn.Journal of neurochemistry · 2012Article
- Deletion of Dlx1 results in reduced glutamatergic input to hippocampal interneurons.Journal of neurophysiology · 2011Article
- Differential localization and function of GABA transporters, GAT-1 and GAT-3, in the rat globus pallidus.The European journal of neuroscience · 2011Article
- The etiological role of blood-brain barrier dysfunction in seizure disorders.Cardiovascular psychiatry and neurology · 2011Article
- Inhibitory inputs to hippocampal interneurons are reorganized in Lis1 mutant mice.Journal of neurophysiology · 2009Article
- Abnormal network activity in a targeted genetic model of human double cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Early cerebrovascular and parenchymal events following prenatal exposure to the putative neurotoxin methylazoxymethanol.Neurobiology of disease · 2007Article
- GABAergic synaptic inhibition is reduced before seizure onset in a genetic model of cortical malformation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2006Article
- Article
- Cortical inhibition modified by embryonic neural precursors grafted into the postnatal brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2006Article
- Dysfunction of synaptic inhibition in epilepsy associated with focal cortical dysplasia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2005Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Children with brain malformations often exhibit an intractable form of epilepsy. Although alterations in cellular physiology and abnormal histology associated with brain malformations has been studied extensively, synaptic function in malformed brain regions remains poorly understood. We used an animal model, rats exposed to methylazoxymethanol (MAM) in utero, featuring loss of lamination and distinct nodular heterotopia to examine inhibitory synaptic function in the malformed brain. Previous in vitro and in vivo studies demonstrated an enhanced susceptibility to seizure activity and neuronal hyperexcitability in these animals. Here we demonstrate that inhibitory synaptic function is enhanced in rats exposed to MAM in utero. Using in vitro hippocampal slices and whole-cell voltage-clamp recordings from visualized neurons, we observed a dramatic prolongation of GABAergic IPSCs onto heterotopic neurons. Spontaneous IPSC decay time constants were increased by 195% and evoked IPSC decay time constants by 220% compared with age-matched control CA1 pyramidal cells; no change in IPSC amplitude or rise time was observed. GABA transport inhibitors (tiagabine and NO-711) prolonged evoked IPSC decay kinetics of control CA1 pyramidal cells (or normotopic cells) but had no effect on heterotopic neurons. Immunohistochemical staining for GABA transporters (GAT-1 and GAT-3) revealed a low level of expression in heterotopic cell regions, suggesting a reduced ability for GABA reuptake at these synapses. Together, our data demonstrate that GABA-mediated synaptic function at heterotopic synapses is altered and suggests that inhibitory systems are enhanced in the malformed brain.
Indexed as
Identifiers
12196583PMC6757980W2114965533What OpenQuestion holds
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.