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Vasoactive intestinal peptide-expressing interneurons are impaired in a mouse model of Dravet syndrome
by
Goldberg, Ethan M
, Goff, Kevin M
in
Acetylcholine receptors (muscarinic)
/ Action Potentials - genetics
/ Action Potentials - physiology
/ Animals
/ Brain - metabolism
/ Brain - physiopathology
/ Brain slice preparation
/ electrophysiology
/ Epilepsies, Myoclonic - genetics
/ Epilepsies, Myoclonic - metabolism
/ Epilepsies, Myoclonic - physiopathology
/ Epilepsy
/ Excitability
/ Firing pattern
/ GABA
/ Genes
/ Health aspects
/ Interneurons
/ Interneurons - metabolism
/ Interneurons - physiology
/ Intestine
/ ion channels
/ Medicine
/ Mice, 129 Strain
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Mice, Transgenic
/ Nav1.1
/ NAV1.1 Voltage-Gated Sodium Channel - genetics
/ NAV1.1 Voltage-Gated Sodium Channel - metabolism
/ Neurodevelopmental disorders
/ Neuroscience
/ Parvalbumin
/ Peptides
/ Physiological aspects
/ Potassium channels (voltage-gated)
/ Receptor mechanisms
/ SCN1A
/ Sodium
/ Sodium channels (voltage-gated)
/ Somatostatin
/ Vasoactive agents
/ Vasoactive intestinal peptide
/ Vasoactive Intestinal Peptide - genetics
/ Vasoactive Intestinal Peptide - metabolism
/ Vasoactive intestinal peptides
/ γ-Aminobutyric acid
2019
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Vasoactive intestinal peptide-expressing interneurons are impaired in a mouse model of Dravet syndrome
by
Goldberg, Ethan M
, Goff, Kevin M
in
Acetylcholine receptors (muscarinic)
/ Action Potentials - genetics
/ Action Potentials - physiology
/ Animals
/ Brain - metabolism
/ Brain - physiopathology
/ Brain slice preparation
/ electrophysiology
/ Epilepsies, Myoclonic - genetics
/ Epilepsies, Myoclonic - metabolism
/ Epilepsies, Myoclonic - physiopathology
/ Epilepsy
/ Excitability
/ Firing pattern
/ GABA
/ Genes
/ Health aspects
/ Interneurons
/ Interneurons - metabolism
/ Interneurons - physiology
/ Intestine
/ ion channels
/ Medicine
/ Mice, 129 Strain
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Mice, Transgenic
/ Nav1.1
/ NAV1.1 Voltage-Gated Sodium Channel - genetics
/ NAV1.1 Voltage-Gated Sodium Channel - metabolism
/ Neurodevelopmental disorders
/ Neuroscience
/ Parvalbumin
/ Peptides
/ Physiological aspects
/ Potassium channels (voltage-gated)
/ Receptor mechanisms
/ SCN1A
/ Sodium
/ Sodium channels (voltage-gated)
/ Somatostatin
/ Vasoactive agents
/ Vasoactive intestinal peptide
/ Vasoactive Intestinal Peptide - genetics
/ Vasoactive Intestinal Peptide - metabolism
/ Vasoactive intestinal peptides
/ γ-Aminobutyric acid
2019
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Vasoactive intestinal peptide-expressing interneurons are impaired in a mouse model of Dravet syndrome
by
Goldberg, Ethan M
, Goff, Kevin M
in
Acetylcholine receptors (muscarinic)
/ Action Potentials - genetics
/ Action Potentials - physiology
/ Animals
/ Brain - metabolism
/ Brain - physiopathology
/ Brain slice preparation
/ electrophysiology
/ Epilepsies, Myoclonic - genetics
/ Epilepsies, Myoclonic - metabolism
/ Epilepsies, Myoclonic - physiopathology
/ Epilepsy
/ Excitability
/ Firing pattern
/ GABA
/ Genes
/ Health aspects
/ Interneurons
/ Interneurons - metabolism
/ Interneurons - physiology
/ Intestine
/ ion channels
/ Medicine
/ Mice, 129 Strain
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Mice, Transgenic
/ Nav1.1
/ NAV1.1 Voltage-Gated Sodium Channel - genetics
/ NAV1.1 Voltage-Gated Sodium Channel - metabolism
/ Neurodevelopmental disorders
/ Neuroscience
/ Parvalbumin
/ Peptides
/ Physiological aspects
/ Potassium channels (voltage-gated)
/ Receptor mechanisms
/ SCN1A
/ Sodium
/ Sodium channels (voltage-gated)
/ Somatostatin
/ Vasoactive agents
/ Vasoactive intestinal peptide
/ Vasoactive Intestinal Peptide - genetics
/ Vasoactive Intestinal Peptide - metabolism
/ Vasoactive intestinal peptides
/ γ-Aminobutyric acid
2019
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Vasoactive intestinal peptide-expressing interneurons are impaired in a mouse model of Dravet syndrome
Journal Article
Vasoactive intestinal peptide-expressing interneurons are impaired in a mouse model of Dravet syndrome
2019
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Overview
Dravet Syndrome (DS) is a severe neurodevelopmental disorder caused by pathogenic loss of function variants in the gene SCN1A which encodes the voltage gated sodium (Na+) channel subunit Nav1.1. GABAergic interneurons expressing parvalbumin (PV-INs) and somatostatin (SST-INs) exhibit impaired excitability in DS (Scn1a+/-) mice. However, the function of a third major class of interneurons in DS – those expressing vasoactive intestinal peptide (VIP-IN) –is unknown. We recorded VIP-INs in brain slices from Scn1a+/-mice and wild-type littermate controls and found prominent impairment of irregular spiking (IS), but not continuous adapting (CA) VIP-INs, in Scn1a+/- mice. Application of the Nav1.1-specific toxin Hm1a rescued the observed deficits. The IS vs. CA firing pattern is determined by expression of KCNQ channels; IS VIP-INs switched to tonic firing with both pharmacologic blockade of M-current and muscarinic acetylcholine receptor activation. These results show that VIP-INs express Nav1.1 and are dysfunctional in DS, which may contribute to DS pathogenesis.
Publisher
eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
Subject
Acetylcholine receptors (muscarinic)
/ Action Potentials - genetics
/ Action Potentials - physiology
/ Animals
/ Epilepsies, Myoclonic - genetics
/ Epilepsies, Myoclonic - metabolism
/ Epilepsies, Myoclonic - physiopathology
/ Epilepsy
/ GABA
/ Genes
/ Medicine
/ Nav1.1
/ NAV1.1 Voltage-Gated Sodium Channel - genetics
/ NAV1.1 Voltage-Gated Sodium Channel - metabolism
/ Neurodevelopmental disorders
/ Peptides
/ Potassium channels (voltage-gated)
/ SCN1A
/ Sodium
/ Sodium channels (voltage-gated)
/ Vasoactive intestinal peptide
/ Vasoactive Intestinal Peptide - genetics
/ Vasoactive Intestinal Peptide - metabolism
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