ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Excitatory effects of parvalbumin-expressing interneurons maintain hippocampal epileptiform activity via synchronous afterdischarges.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed.
- WNK-SPAK/OSR1 signaling pathway facilitates ictal activity via reduced neuronal chloride extrusion rate.bioRxiv : the preprint server for biology · 2026Article
- Neuron-derived neurotrophic factor-positive interneurons: a cellular target for anti-seizure therapies.EBioMedicine · 2026Article
- Enhancing KCC2 function reduces interictal activity and prevents seizures in temporal lobe epilepsy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Electrophysiologically Targeted Biopsies Reveal the Transcriptional Landscape of Focal Epilepsy.bioRxiv : the preprint server for biology · 2026Article
- Dysfunction of GABAergic interneurons underlies altered neural network oscillations associated with epileptiform activity in PPT1-deficient mice.Translational psychiatry · 2026Article
- Massive Activation of GABABiomolecules · 2025Review
- Rodent and human seizures demonstrate a dynamic interplay with spreading depolarizations.Neurobiology of disease · 2025Article
- H- and m-channel overexpression promotes seizure-like events by impairing the ability of inhibitory neurons to process correlated inputs.PLoS computational biology · 2025Article
- Somatic mosaicism and interneuron involvement in mTORopathies.Trends in neurosciences · 2025Review
- Article
- Activation of hypoactive parvalbumin-positive fast-spiking interneurons restores dentate inhibition to reduce electrographic seizures in the mouse intrahippocampal kainate model of temporal lobe epilepsy.Neurobiology of disease · 2024Article
- All-optical reporting of inhibitory receptor driving force in the nervous system.Nature communications · 2024Article
- Optogenetic Determination of Dynamic and Cell-Type-Specific Inhibitory Reversal Potentials.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Dialectics of perisomatic inhibition-The unity and conflict of opposites.Frontiers in neural circuits · 2024Review
- Reclusive chandeliers: Functional isolation of dentate axo-axonic cells after experimental status epilepticus.Progress in neurobiology · 2023Article
- Cell-type specific and multiscale dynamics of human focal seizures in limbic structures.Brain : a journal of neurology · 2023Article
- Daily rhythm in cortical chloride homeostasis underpins functional changes in visual cortex excitability.Nature communications · 2023Article
- Reduced Cholecystokinin-Expressing Interneuron Input Contributes to Disinhibition of the Hippocampal CA2 Region in a Mouse Model of Temporal Lobe Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- RECLUSIVE CHANDELIERS: FUNCTIONAL ISOLATION OF DENTATE AXO-AXONIC CELLS AFTER EXPERIMENTAL STATUS EPILEPTICUS.bioRxiv : the preprint server for biology · 2023Article
- Optogenetic stimulation reveals a latent tipping point in cortical networks during ictogenesis.Brain : a journal of neurology · 2023Article
44 more citing papers are in PubMed but not listed here.
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5 authors.
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Abstract
Epileptic seizures are characterized by periods of hypersynchronous, hyperexcitability within brain networks. Most seizures involve two stages: an initial tonic phase, followed by a longer clonic phase that is characterized by rhythmic bouts of synchronized network activity called afterdischarges (ADs). Here we investigate the cellular and network mechanisms underlying hippocampal ADs in an effort to understand how they maintain seizure activity. Using in vitro hippocampal slice models from rats and mice, we performed electrophysiological recordings from CA3 pyramidal neurons to monitor network activity and changes in GABAergic signaling during epileptiform activity. First, we show that the highest synchrony occurs during clonic ADs, consistent with the idea that specific circuit dynamics underlie this phase of the epileptiform activity. We then show that ADs require intact GABAergic synaptic transmission, which becomes excitatory as a result of a transient collapse in the chloride (Cl(-)) reversal potential. The depolarizing effects of GABA are strongest at the soma of pyramidal neurons, which implicates somatic-targeting interneurons in AD activity. To test this, we used optogenetic techniques to selectively control the activity of somatic-targeting parvalbumin-expressing (PV(+)) interneurons. Channelrhodopsin-2-mediated activation of PV(+) interneurons during the clonic phase generated excitatory GABAergic responses in pyramidal neurons, which were sufficient to elicit and entrain synchronous AD activity across the network. Finally, archaerhodopsin-mediated selective silencing of PV(+) interneurons reduced the occurrence of ADs during the clonic phase. Therefore, we propose that activity-dependent Cl(-) accumulation subverts the actions of PV(+) interneurons to perpetuate rather than terminate pathological network hyperexcitability during the clonic phase of seizures.
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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.