Mitochondrial Regulation of the Hippocampal Firing Rate Set Point and Seizure Susceptibility

Boaz Styr; Nir Gonen; Daniel Zarhin; Antonella Ruggiero; Refaela Atsmon; Neta Gazit; Gabriella Braun; Samuel Frere; Irena Vertkin; Ilana Shapira; Michal Harel; Leore R. Heim; Maxim Katsenelson; Ohad Rechnitz; Saja Fadila; Dori Derdikman; Moran Rubinstein; Tamar Geiger; Eytan Ruppin; Inna Slutsky

doi:10.1016/j.neuron.2019.03.045

Mitochondrial Regulation of the Hippocampal Firing Rate Set Point and Seizure Susceptibility

Boaz Styr, Nir Gonen, Daniel Zarhin, Antonella Ruggiero, Refaela Atsmon, Neta Gazit, Gabriella Braun, Samuel Frere, Irena Vertkin, Ilana Shapira, Michal Harel, Leore R. Heim, Maxim Katsenelson, Ohad Rechnitz, Saja Fadila, Dori Derdikman, Moran Rubinstein, Tamar Geiger, Eytan Ruppin, Inna Slutsky^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

Abstract

Firing rate set-point regulation has puzzled researchers for decades. Our findings show that mitochondrial DHODH meets the criteria of a bone fide regulator of activity set points and suggest lowering firing set point as a new strategy to treat epilepsy.

Original language	English
Pages (from-to)	1009-1024.e8
Journal	Neuron
Volume	102
Issue number	5
DOIs	https://doi.org/10.1016/j.neuron.2019.03.045
State	Published - 5 Jun 2019

Funding

Funders	Funder number
National Cancer Institute	ZIABC011802
European Research Council	724866
Rosetrees Trust
Ministry of Science, Technology and Space
Israel Science Foundation	1849/17, 1663/18
Porter School of Environmental Studies, Tel Aviv University
Azrieli Foundation

Keywords

Dravet syndrome
calcium
dihydroorotate dehydrogenase
epilepsy
firing rate
hippocampus
homeostasis
mitochondria
neuronal metabolism
set point

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10.1016/j.neuron.2019.03.045

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Styr, B., Gonen, N., Zarhin, D., Ruggiero, A., Atsmon, R., Gazit, N., Braun, G., Frere, S., Vertkin, I., Shapira, I., Harel, M., Heim, L. R., Katsenelson, M., Rechnitz, O., Fadila, S., Derdikman, D., Rubinstein, M., Geiger, T., Ruppin, E., & Slutsky, I. (2019). Mitochondrial Regulation of the Hippocampal Firing Rate Set Point and Seizure Susceptibility. Neuron, 102(5), 1009-1024.e8. https://doi.org/10.1016/j.neuron.2019.03.045

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title = "Mitochondrial Regulation of the Hippocampal Firing Rate Set Point and Seizure Susceptibility",

abstract = "Firing rate set-point regulation has puzzled researchers for decades. Our findings show that mitochondrial DHODH meets the criteria of a bone fide regulator of activity set points and suggest lowering firing set point as a new strategy to treat epilepsy.",

keywords = "Dravet syndrome, calcium, dihydroorotate dehydrogenase, epilepsy, firing rate, hippocampus, homeostasis, mitochondria, neuronal metabolism, set point",

author = "Boaz Styr and Nir Gonen and Daniel Zarhin and Antonella Ruggiero and Refaela Atsmon and Neta Gazit and Gabriella Braun and Samuel Frere and Irena Vertkin and Ilana Shapira and Michal Harel and Heim, {Leore R.} and Maxim Katsenelson and Ohad Rechnitz and Saja Fadila and Dori Derdikman and Moran Rubinstein and Tamar Geiger and Eytan Ruppin and Inna Slutsky",

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Styr, B, Gonen, N, Zarhin, D, Ruggiero, A, Atsmon, R, Gazit, N, Braun, G, Frere, S, Vertkin, I, Shapira, I, Harel, M, Heim, LR, Katsenelson, M, Rechnitz, O, Fadila, S, Derdikman, D, Rubinstein, M , Geiger, T , Ruppin, E & Slutsky, I 2019, 'Mitochondrial Regulation of the Hippocampal Firing Rate Set Point and Seizure Susceptibility', Neuron, vol. 102, no. 5, pp. 1009-1024.e8. https://doi.org/10.1016/j.neuron.2019.03.045

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AU - Atsmon, Refaela

AU - Gazit, Neta

AU - Braun, Gabriella

AU - Frere, Samuel

AU - Vertkin, Irena

AU - Shapira, Ilana

AU - Harel, Michal

AU - Heim, Leore R.

AU - Katsenelson, Maxim

AU - Rechnitz, Ohad

AU - Fadila, Saja

AU - Derdikman, Dori

AU - Rubinstein, Moran

AU - Geiger, Tamar

AU - Ruppin, Eytan

AU - Slutsky, Inna

PY - 2019/6/5

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KW - dihydroorotate dehydrogenase

KW - epilepsy

KW - firing rate

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KW - homeostasis

KW - mitochondria

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Mitochondrial Regulation of the Hippocampal Firing Rate Set Point and Seizure Susceptibility

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