ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
GABAergic synaptic inhibition is reduced before seizure onset in a genetic model of cortical malformation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 45 citations in OpenAlex.
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- A deletion in Eml1 leads to bilateral subcortical heterotopia in the tish rat.Neurobiology of disease · 2020Article
- Interneuron Desynchronization Precedes Seizures in a Mouse Model of Dravet Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Neuronal migration disorders: Focus on the cytoskeleton and epilepsy.Neurobiology of disease · 2016Review
- Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy.Progress in brain research · 2016Review
- Neonatal and Infantile Epilepsy: Acquired and Genetic Models.Cold Spring Harbor perspectives in medicine · 2015Review
- Initiation, Propagation, and Termination of Partial (Focal) Seizures.Cold Spring Harbor perspectives in medicine · 2015Review
- Simulating vertical and horizontal inhibition with short-term dynamics in a multi-column multi-layer model of neocortex.International journal of neural systems · 2014Article
- Early susceptibility for epileptiform activity in malformed cortex.Epilepsy research · 2014Article
- Bilateral subcortical heterotopia with partial callosal agenesis in a mouse mutant.Cerebral cortex (New York, N.Y. : 1991) · 2013Article
- LIS1 deficiency promotes dysfunctional synaptic integration of granule cells generated in the developing and adult dentate gyrus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Functional alterations in GABAergic fast-spiking interneurons in chronically injured epileptogenic neocortex.Neurobiology of disease · 2012Article
- Transition to seizure: ictal discharge is preceded by exhausted presynaptic GABA release in the hippocampal CA3 region.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Reorganization of inhibitory synaptic circuits in rodent chronically injured epileptogenic neocortex.Cerebral cortex (New York, N.Y. : 1991) · 2011Article
- Deletion of Dlx1 results in reduced glutamatergic input to hippocampal interneurons.Journal of neurophysiology · 2011Article
- Layer I neocortical ectopia: cellular organization and local cortical circuitry.Brain research · 2011Article
- Altered intrinsic properties of neuronal subtypes in malformed epileptogenic cortex.Brain research · 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
- Light-induced rescue of breathing after spinal cord injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2008Article
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4 authors at 1 institution in 1 country.
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Abstract
Malformations of the neocortex are a common cause of human epilepsy; however, the critical issue of how disturbances in cortical organization render neurons epileptogenic remains controversial. The present study addressed this issue by studying inhibitory structure and function before seizure onset in the telencephalic internal structural heterotopia (tish) rat, which is a genetic model of heightened seizure susceptibility associated with a prominent neocortical malformation. Both normally positioned (normotopic) and misplaced (heterotopic) pyramidal neurons in the tish neocortex exhibited lower resting membrane potentials and a tendency toward higher input resistance compared with pyramidal neurons from control brains. GABAergic synaptic transmission was attenuated in the tish cortex, characterized by significant reductions in the frequency of spontaneous IPSCs (sIPSCs) and miniature IPSCs recorded from pyramidal neurons. In addition, the amplitudes of sIPSCs were reduced in the tish neocortex, an effect that was more profound in the normotopic cells. Immunohistochemical assessment of presynaptic GABAergic terminals showed a reduction in terminals surrounding pyramidal cell somata in normotopic and heterotopic tish neocortex. The attenuation of inhibitory innervation was more prominent for normotopic neurons and was associated with a reduction in a subset of GABAergic interneurons expressing the calcium-binding protein parvalbumin. Together, these findings indicate that key facets of inhibitory GABAergic neurotransmission are disturbed before seizure onset in a brain predisposed to developing seizures. Such alterations represent a rational substrate for reduced seizure thresholds associated with certain cortical malformations.
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