The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice. / von Schoubye, Nadia Lybøl; Frederiksen, Kristen; Kristiansen, Uffe; Petersen, Anders Victor; Dalby, Nils Ole; Grunnet, Morten; Jensen, Henrik Sindal; Jespersen, Thomas; Sohal, Vikaas S; Perrier, Jean-François.

In: Neuroscience Letters, Vol. 662, 2018, p. 29-35.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

von Schoubye, NL, Frederiksen, K, Kristiansen, U, Petersen, AV, Dalby, NO, Grunnet, M, Jensen, HS, Jespersen, T, Sohal, VS & Perrier, J-F 2018, 'The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice', Neuroscience Letters, vol. 662, pp. 29-35. https://doi.org/10.1016/j.neulet.2017.10.004

APA

von Schoubye, N. L., Frederiksen, K., Kristiansen, U., Petersen, A. V., Dalby, N. O., Grunnet, M., Jensen, H. S., Jespersen, T., Sohal, V. S., & Perrier, J-F. (2018). The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice. Neuroscience Letters, 662, 29-35. https://doi.org/10.1016/j.neulet.2017.10.004

Vancouver

von Schoubye NL, Frederiksen K, Kristiansen U, Petersen AV, Dalby NO, Grunnet M et al. The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice. Neuroscience Letters. 2018;662:29-35. https://doi.org/10.1016/j.neulet.2017.10.004

Author

von Schoubye, Nadia Lybøl ; Frederiksen, Kristen ; Kristiansen, Uffe ; Petersen, Anders Victor ; Dalby, Nils Ole ; Grunnet, Morten ; Jensen, Henrik Sindal ; Jespersen, Thomas ; Sohal, Vikaas S ; Perrier, Jean-François. / The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice. In: Neuroscience Letters. 2018 ; Vol. 662. pp. 29-35.

Bibtex

@article{88b6ef24e8ae4bea8a4c60ed276de7ea,
title = "The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice",
abstract = "Mental disorders such as schizophrenia are associated with impaired firing properties of fast spiking inhibitory interneurons (FSINs) causing reduced task-evoked gamma-oscillation in prefrontal cortex. The voltage-gated sodium channel NaV1.1 is highly expressed in PV-positive interneurons, but only at low levels in principal cells. Positive modulators of Nav1.1 channels are for this reason considered potential candidates for the treatment of cognitive disorders. Here we examined the effect of the novel positive modulator of voltage-gated sodium channels Lu AE98134. We found that Lu AE98134 facilitated the sodium current mediated by NaV1.1 expressed in HEK cells by shifting its activation to more negative values, decreasing its inactivation kinetics and promoting a persistent inward current. In a slice preparation from the brain of adult mice, Lu AE98134 promoted the excitability of fast spiking interneurons by decreasing the threshold for action potentials. We then tested if Lu AE98134 could normalize the altered firing properties of FSINs in Dlx5/6+/- mutant mice. FSINs of this model for schizophrenia are characterized by broader action potentials and higher spike threshold. We found that in the presence of Lu AE98134, the firing frequency was increased while the spike duration and the threshold were decreased. Compounds with similar mode of action appear as promising candidates for restoring cognitive deficits present in schizophrenia.",
keywords = "Journal Article",
author = "{von Schoubye}, {Nadia Lyb{\o}l} and Kristen Frederiksen and Uffe Kristiansen and Petersen, {Anders Victor} and Dalby, {Nils Ole} and Morten Grunnet and Jensen, {Henrik Sindal} and Thomas Jespersen and Sohal, {Vikaas S} and Jean-Fran{\c c}ois Perrier",
note = "Copyright {\textcopyright} 2017 Elsevier B.V. All rights reserved.",
year = "2018",
doi = "10.1016/j.neulet.2017.10.004",
language = "English",
volume = "662",
pages = "29--35",
journal = "Neuroscience letters. Supplement",
issn = "0167-6253",
publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice

AU - von Schoubye, Nadia Lybøl

AU - Frederiksen, Kristen

AU - Kristiansen, Uffe

AU - Petersen, Anders Victor

AU - Dalby, Nils Ole

AU - Grunnet, Morten

AU - Jensen, Henrik Sindal

AU - Jespersen, Thomas

AU - Sohal, Vikaas S

AU - Perrier, Jean-François

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2018

Y1 - 2018

N2 - Mental disorders such as schizophrenia are associated with impaired firing properties of fast spiking inhibitory interneurons (FSINs) causing reduced task-evoked gamma-oscillation in prefrontal cortex. The voltage-gated sodium channel NaV1.1 is highly expressed in PV-positive interneurons, but only at low levels in principal cells. Positive modulators of Nav1.1 channels are for this reason considered potential candidates for the treatment of cognitive disorders. Here we examined the effect of the novel positive modulator of voltage-gated sodium channels Lu AE98134. We found that Lu AE98134 facilitated the sodium current mediated by NaV1.1 expressed in HEK cells by shifting its activation to more negative values, decreasing its inactivation kinetics and promoting a persistent inward current. In a slice preparation from the brain of adult mice, Lu AE98134 promoted the excitability of fast spiking interneurons by decreasing the threshold for action potentials. We then tested if Lu AE98134 could normalize the altered firing properties of FSINs in Dlx5/6+/- mutant mice. FSINs of this model for schizophrenia are characterized by broader action potentials and higher spike threshold. We found that in the presence of Lu AE98134, the firing frequency was increased while the spike duration and the threshold were decreased. Compounds with similar mode of action appear as promising candidates for restoring cognitive deficits present in schizophrenia.

AB - Mental disorders such as schizophrenia are associated with impaired firing properties of fast spiking inhibitory interneurons (FSINs) causing reduced task-evoked gamma-oscillation in prefrontal cortex. The voltage-gated sodium channel NaV1.1 is highly expressed in PV-positive interneurons, but only at low levels in principal cells. Positive modulators of Nav1.1 channels are for this reason considered potential candidates for the treatment of cognitive disorders. Here we examined the effect of the novel positive modulator of voltage-gated sodium channels Lu AE98134. We found that Lu AE98134 facilitated the sodium current mediated by NaV1.1 expressed in HEK cells by shifting its activation to more negative values, decreasing its inactivation kinetics and promoting a persistent inward current. In a slice preparation from the brain of adult mice, Lu AE98134 promoted the excitability of fast spiking interneurons by decreasing the threshold for action potentials. We then tested if Lu AE98134 could normalize the altered firing properties of FSINs in Dlx5/6+/- mutant mice. FSINs of this model for schizophrenia are characterized by broader action potentials and higher spike threshold. We found that in the presence of Lu AE98134, the firing frequency was increased while the spike duration and the threshold were decreased. Compounds with similar mode of action appear as promising candidates for restoring cognitive deficits present in schizophrenia.

KW - Journal Article

U2 - 10.1016/j.neulet.2017.10.004

DO - 10.1016/j.neulet.2017.10.004

M3 - Journal article

C2 - 28987817

VL - 662

SP - 29

EP - 35

JO - Neuroscience letters. Supplement

JF - Neuroscience letters. Supplement

SN - 0167-6253

ER -

ID: 186876130