Impaired excitability of fast-spiking neurons in a novel mouse model ofKCNC1epileptic encephalopathy

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 27, 2024

The recurrent pathogenic variant

Language: Английский

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Impaired excitability of fast-spiking neurons in a novel mouse model of KCNC1 epileptic encephalopathy

Published: Dec. 2, 2024

The recurrent pathogenic variant KCNC1 -p.Ala421Val (A421V) is a cause of developmental and epileptic encephalopathy characterized by moderate-to-severe delay/intellectual disability, infantile-onset treatment-resistant epilepsy with multiple seizure types including myoclonic seizures. Yet, the mechanistic basis disease unclear. encodes Kv3.1, voltage-gated potassium channel subunit that highly selectively expressed in neurons capable generating action potentials at high frequency, parvalbumin-positive fast-spiking GABAergic inhibitory interneurons cerebral cortex (PV-INs) known to be important for cognitive function plasticity as well control network excitation prevent In this study, we generate novel transgenic mouse model conditional expression Ala421Val missense ( Kcnc1 -A421V/+ mice) explore physiological mechanisms encephalopathy. Our results indicate global heterozygous A421V leads premature lethality. We observe decreased PV-IN cell surface Kv3.1 via immunohistochemistry, current density PV-INs using outside-out nucleated macropatch recordings brain slice, profound impairments intrinsic excitability but not excitatory current-clamp electrophysiology. vivo two-photon calcium imaging revealed hypersynchronous discharges correlated brief paroxysmal movements, subsequently shown seizures on electroencephalography. found alterations PV-IN-mediated neurotransmission young adult juvenile mice relative wild-type controls. Together, these establish impact Kv3.1-A421V neuronal synaptic physiology across development drive dysfunction underlying

Language: Английский

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Impaired excitability of fast-spiking neurons in a novel mouse model of KCNC1 epileptic encephalopathy

Published: Dec. 2, 2024

The recurrent pathogenic variant KCNC1 -p.Ala421Val (A421V) is a cause of developmental and epileptic encephalopathy characterized by moderate-to-severe delay/intellectual disability, infantile-onset treatment-resistant epilepsy with multiple seizure types including myoclonic seizures. Yet, the mechanistic basis disease unclear. encodes Kv3.1, voltage-gated potassium channel subunit that highly selectively expressed in neurons capable generating action potentials at high frequency, parvalbumin-positive fast-spiking GABAergic inhibitory interneurons cerebral cortex (PV-INs) known to be important for cognitive function plasticity as well control network excitation prevent In this study, we generate novel transgenic mouse model conditional expression Ala421Val missense ( Kcnc1 -A421V/+ mice) explore physiological mechanisms encephalopathy. Our results indicate global heterozygous A421V leads premature lethality. We observe decreased PV-IN cell surface Kv3.1 via immunohistochemistry, current density PV-INs using outside-out nucleated macropatch recordings brain slice, profound impairments intrinsic excitability but not excitatory current-clamp electrophysiology. vivo two-photon calcium imaging revealed hypersynchronous discharges correlated brief paroxysmal movements, subsequently shown seizures on electroencephalography. found alterations PV-IN-mediated neurotransmission young adult juvenile mice relative wild-type controls. Together, these establish impact Kv3.1-A421V neuronal synaptic physiology across development drive dysfunction underlying

Language: Английский

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‘VIP’ interneurons may govern autism traits in Dravet syndrome

The Transmitter, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

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Unspooling the Thread: VIP Interneurons Linked With Autism Spectrum Disorder Behaviors but Not Seizures in Dravet Syndrome

Epiliepsy currents/Epilepsy currents, Journal Year: 2023, Volume and Issue: 24(1), P. 62 - 64

Published: Dec. 27, 2023

[Box: see text]

Language: Английский

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