CaV2.3 Channels Are Critical for Oscillatory Burst Discharges in the Reticular Thalamus and Absence Epilepsy

Tariq Zaman; Kyoobin Lee; Cheongdahm Park; Afshin Paydar; Jee Hyun Choi; Eunji Cheong; C. Justin Lee; Hee Sup Shin

doi:10.1016/j.neuron.2011.02.042

Ca_V2.3 Channels Are Critical for Oscillatory Burst Discharges in the Reticular Thalamus and Absence Epilepsy

Tariq Zaman, Kyoobin Lee, Cheongdahm Park, Afshin Paydar, Jee Hyun Choi, Eunji Cheong, C. Justin Lee, Hee Sup Shin

KU-KIST Graduate School of Converging Science and Technology

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

64 Citations (Scopus)

Abstract

Neurons of the reticular thalamus (RT) display oscillatory burst discharges that are believed to be critical for thalamocortical network oscillations related to absence epilepsy. Ca²⁺-dependent mechanisms underlie such oscillatory discharges. However, involvement of high-voltage activated (HVA) Ca²⁺ channels in this process has been discounted. We examined this issue closely using mice deficient for the HVA Ca_V2.3 channels. In brain slices of Ca_V2.3^-/-, a hyperpolarizing current injection initiated a low-threshold burst of spikes in RT neurons; however, subsequent oscillatory burst discharges were severely suppressed, with a significantly reduced slow afterhyperpolarization (AHP). Consequently, the lack of Ca_V2.3 resulted in a marked decrease in the sensitivity of the animal to γ-butyrolactone-induced absence epilepsy. Local blockade of Ca_V2.3 channels in the RT mimicked the results of Ca_V2.3^-/- mice. These results provide strong evidence that Ca_V2.3 channels are critical for oscillatory burst discharges in RT neurons and for the expression of absence epilepsy.

Original language	English
Pages (from-to)	95-108
Number of pages	14
Journal	Neuron
Volume	70
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2011.02.042
Publication status	Published - 2011 Apr 14

Bibliographical note

Funding Information:
We thank Chanki Kim, M.A. Aslam, Gireesh G., Sungsoo Jang, Soojung Lee, Il-hwan Choe, and Seung-eun Lee for technical as well as intellectual support. This work was supported by the National Honor Scientist Program of the Korean Government, and the WCI program of Korea Institute of Science and Technology.

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/j.neuron.2011.02.042

Cite this

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title = "CaV2.3 Channels Are Critical for Oscillatory Burst Discharges in the Reticular Thalamus and Absence Epilepsy",

abstract = "Neurons of the reticular thalamus (RT) display oscillatory burst discharges that are believed to be critical for thalamocortical network oscillations related to absence epilepsy. Ca2+-dependent mechanisms underlie such oscillatory discharges. However, involvement of high-voltage activated (HVA) Ca2+ channels in this process has been discounted. We examined this issue closely using mice deficient for the HVA CaV2.3 channels. In brain slices of CaV2.3-/-, a hyperpolarizing current injection initiated a low-threshold burst of spikes in RT neurons; however, subsequent oscillatory burst discharges were severely suppressed, with a significantly reduced slow afterhyperpolarization (AHP). Consequently, the lack of CaV2.3 resulted in a marked decrease in the sensitivity of the animal to γ-butyrolactone-induced absence epilepsy. Local blockade of CaV2.3 channels in the RT mimicked the results of CaV2.3-/- mice. These results provide strong evidence that CaV2.3 channels are critical for oscillatory burst discharges in RT neurons and for the expression of absence epilepsy.",

author = "Tariq Zaman and Kyoobin Lee and Cheongdahm Park and Afshin Paydar and Choi, {Jee Hyun} and Eunji Cheong and Lee, {C. Justin} and Shin, {Hee Sup}",

note = "Funding Information: We thank Chanki Kim, M.A. Aslam, Gireesh G., Sungsoo Jang, Soojung Lee, Il-hwan Choe, and Seung-eun Lee for technical as well as intellectual support. This work was supported by the National Honor Scientist Program of the Korean Government, and the WCI program of Korea Institute of Science and Technology. ",

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AU - Zaman, Tariq

AU - Lee, Kyoobin

AU - Park, Cheongdahm

AU - Paydar, Afshin

AU - Choi, Jee Hyun

AU - Cheong, Eunji

AU - Lee, C. Justin

AU - Shin, Hee Sup

N1 - Funding Information: We thank Chanki Kim, M.A. Aslam, Gireesh G., Sungsoo Jang, Soojung Lee, Il-hwan Choe, and Seung-eun Lee for technical as well as intellectual support. This work was supported by the National Honor Scientist Program of the Korean Government, and the WCI program of Korea Institute of Science and Technology.

PY - 2011/4/14

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N2 - Neurons of the reticular thalamus (RT) display oscillatory burst discharges that are believed to be critical for thalamocortical network oscillations related to absence epilepsy. Ca2+-dependent mechanisms underlie such oscillatory discharges. However, involvement of high-voltage activated (HVA) Ca2+ channels in this process has been discounted. We examined this issue closely using mice deficient for the HVA CaV2.3 channels. In brain slices of CaV2.3-/-, a hyperpolarizing current injection initiated a low-threshold burst of spikes in RT neurons; however, subsequent oscillatory burst discharges were severely suppressed, with a significantly reduced slow afterhyperpolarization (AHP). Consequently, the lack of CaV2.3 resulted in a marked decrease in the sensitivity of the animal to γ-butyrolactone-induced absence epilepsy. Local blockade of CaV2.3 channels in the RT mimicked the results of CaV2.3-/- mice. These results provide strong evidence that CaV2.3 channels are critical for oscillatory burst discharges in RT neurons and for the expression of absence epilepsy.

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