ArticleEpilepsia2015
Muscarinic excitation of parvalbumin-positive interneurons contributes to the severity of pilocarpine-induced seizures.
Article in Epilepsia, 2015. 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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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Circular RNA PTPN4 Contributes to Blood-Brain Barrier Disruption during Early Epileptogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cholinergic Activation of Corticofugal Circuits in the Adult Mouse Prefrontal Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Cell-type specific and multiscale dynamics of human focal seizures in limbic structures.Brain : a journal of neurology · 2023Article
- Effect of ramosetron, a 5-HTThe journal of physiological sciences : JPS · 2022Article
- Differences in Evolution of Epileptic Seizures and Topographical Distribution of Tissue Damage in Selected Limbic Structures Between Male and Female Rats Submitted to the Pilocarpine Model.Frontiers in neurology · 2022Article
- Parvalbumin Role in Epilepsy and Psychiatric Comorbidities: From Mechanism to Intervention.Frontiers in integrative neuroscience · 2022Review
- Control of Brain State Transitions with a Photoswitchable Muscarinic Agonist.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Cholinergic Signaling, Neural Excitability, and Epilepsy.Molecules (Basel, Switzerland) · 2021Review
- Loss of Long-Term Potentiation at Hippocampal Output Synapses in Experimental Temporal Lobe Epilepsy.Frontiers in molecular neuroscience · 2020Article
- Voltage-Dependent Calcium Channels, Calcium Binding Proteins, and Their Interaction in the Pathological Process of Epilepsy.International journal of molecular sciences · 2018Review
- Specificity, Versatility, and Continual Development: The Power of Optogenetics for Epilepsy Research.Frontiers in cellular neuroscience · 2018Review
- Hippocampal GABAergic Inhibitory Interneurons.Physiological reviews · 2017Review
- The influence of depolarization block on seizure-like activity in networks of excitatory and inhibitory neurons.Journal of computational neuroscience · 2017Article
- Synapsin II Regulation of GABAergic Synaptic Transmission Is Dependent on Interneuron Subtype.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- The antiepileptic and ictogenic effects of optogenetic neurostimulation of PV-expressing interneurons.Journal of neurophysiology · 2016Article
- Persistent Hyperactivity of Hippocampal Dentate Interneurons After a Silent Period in the Rat Pilocarpine Model of Epilepsy.Frontiers in cellular neuroscience · 2016Article
- Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy.Progress in brain research · 2016Review
- Brain State Is a Major Factor in Preseizure Hippocampal Network Activity and Influences Success of Seizure Intervention.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Modeling focal epileptic activity in the Wilson-cowan model with depolarization block.Journal of mathematical neuroscience · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveA common rodent model in epilepsy research employs the muscarinic acetylcholine receptor (mAChR) agonist pilocarpine, yet the mechanisms underlying the induction of pilocarpine-induced seizures (PISs) remain unclear. Global M1 mAChR (M1 R) knockout mice are resistant to PISs, implying that M1 R activation disrupts excitation/inhibition balance. Parvalbumin-positive (PV) inhibitory neurons express M1 Rs, participate in cholinergically induced oscillations, and can enter a state of depolarization block (DB) during epileptiform activity. Here, we test the hypothesis that pilocarpine activation of M1 Rs expressed on PV cells contributes to PISs.
methodsCA1 PV cells in PV-CRE mice were visualized with a floxed YFP or hM3Dq-mCherry adeno-associated virus, or by crossing PV-CRE mice with the RosaYFP reporter line. To eliminate M1 Rs from PV cells, we generated PV-M1 knockout (KO) mice by crossing PV-CRE and floxed M1 mice. Action potential (AP) frequency was monitored during application of pilocarpine (200 μm). In behavioral experiments, locomotion and seizure symptoms were recorded in wild-type (WT) or PV-M1 KO mice during PISs.
resultsPilocarpine significantly increased AP frequency in CA1 PV cells into the gamma range. In the continued presence of pilocarpine, a subset (5/7) of PV cells progressed to DB, which was mimicked by hM3Dq activation of Gq-receptor signaling. Pilocarpine-induced depolarization, AP firing at gamma frequency, and progression to DB were prevented in CA1 PV cells of PV-M1 KO mice. Finally, compared to WT mice, PV-M1 KO mice were associated with reduced severity of PISs. SIGNIFICANCE: Pilocarpine can directly depolarize PV+ cells via M1 R activation, but a subset of these cells progress to DB. Our electrophysiologic and behavioral results suggest that this mechanism is active during PISs, contributing to a collapse of PV-mediated γ-aminobutyric acid (GABA)ergic inhibition, dysregulation of excitation/inhibition balance, and increased susceptibility to PISs.
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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.