Motor dysfunction in the tottering mouse is linked to cerebellar spontaneous low frequency oscillations revealed by flavoprotein autofluorescence optical imaging

Gang Chen, Laurentiu S Popa, Xinming Wang, Wangcai Gao, Justin Barnes, Claudia Hendrix, Ellen J. Hess, Timothy J Ebner

Research output: Contribution to journalConference article

Abstract

Flavoprotein autofluorescence optical imaging is developing into a powerful research tool to study neural activity, particularly in vivo. In this study we used this imaging technique to investigate the neuronal mechanism underlying the episodic movement disorder that is characteristic of the tottering (tg) mouse, a model of episodic ataxia type 2. Both EA2 and the tg mouse are caused by mutations in the gene encoding Ca v2.1 (P/Q-type) voltage-gated Ca 2+ channels. These mutations result in a reduction in P/Q Ca 2+ channel function. Both EA2 patients and tg mice have a characteristic phenotype consisting of transient motor attacks triggered by stress, caffeine or ethanol. The neural events underlying these episodes of dystonia are unknown. Flavoprotein autofluorescence optical imaging revealed spontaneous, transient, low frequency oscillations in the cerebellar cortex of the tg mouse. Lasting from 30 - 120 minutes, the oscillations originate in one area then spread to surrounding regions over 30 - 60 minutes. The oscillations are reduced by removing extracellular Ca 2+ and blocking Ca v 1.2/1.3 (L-type) Ca 2+ channels. The oscillations are not affected by blocking AMPA receptors or by electrical stimulation of the parallel fiber - Purkinje cell circuit, suggesting the oscillations are generated intrinsically in the cerebellar cortex. Conversely, L-type Ca 2+ agonists generate oscillations with similar properties. In the awake tg mouse, transcranial flavoprotein imaging revealed low frequency oscillations that are accentuated during caffeine induced attacks of dystonia. The oscillations increase during the attacks of dystonia and are coupled to oscillations in face and hindlimb EMG activity. These transient oscillations and the associated cerebellar dysfunction provide a novel mechanism by which an ion channel disorder results in episodic motor dysfunction.

Original languageEnglish (US)
Article number71800C
JournalProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume7180
DOIs
StatePublished - Jun 1 2009
EventPhotons and Neurons - San Jose, CA, United States
Duration: Jan 25 2009Jan 26 2009

Fingerprint

Autofluorescence
Flavoproteins
Optical Imaging
mice
Low Frequency
Mouse
Oscillation
Dystonia
low frequencies
Caffeine
Imaging techniques
oscillations
Cerebellar Cortex
attack
Gene encoding
AMPA Receptors
caffeine
Cerebellar Diseases
cortexes
Ion Channels

Keywords

  • Autofluorescence
  • Cerebellum
  • Channelopathy
  • Dystonia
  • Episodic ataxia
  • Flavoprotein
  • Optical imaging
  • Oscillation
  • P/Q calcium channels
  • Tottering mouse

Cite this

@article{acbb0b75882a4c50a5232a36ff123adb,
title = "Motor dysfunction in the tottering mouse is linked to cerebellar spontaneous low frequency oscillations revealed by flavoprotein autofluorescence optical imaging",
abstract = "Flavoprotein autofluorescence optical imaging is developing into a powerful research tool to study neural activity, particularly in vivo. In this study we used this imaging technique to investigate the neuronal mechanism underlying the episodic movement disorder that is characteristic of the tottering (tg) mouse, a model of episodic ataxia type 2. Both EA2 and the tg mouse are caused by mutations in the gene encoding Ca v2.1 (P/Q-type) voltage-gated Ca 2+ channels. These mutations result in a reduction in P/Q Ca 2+ channel function. Both EA2 patients and tg mice have a characteristic phenotype consisting of transient motor attacks triggered by stress, caffeine or ethanol. The neural events underlying these episodes of dystonia are unknown. Flavoprotein autofluorescence optical imaging revealed spontaneous, transient, low frequency oscillations in the cerebellar cortex of the tg mouse. Lasting from 30 - 120 minutes, the oscillations originate in one area then spread to surrounding regions over 30 - 60 minutes. The oscillations are reduced by removing extracellular Ca 2+ and blocking Ca v 1.2/1.3 (L-type) Ca 2+ channels. The oscillations are not affected by blocking AMPA receptors or by electrical stimulation of the parallel fiber - Purkinje cell circuit, suggesting the oscillations are generated intrinsically in the cerebellar cortex. Conversely, L-type Ca 2+ agonists generate oscillations with similar properties. In the awake tg mouse, transcranial flavoprotein imaging revealed low frequency oscillations that are accentuated during caffeine induced attacks of dystonia. The oscillations increase during the attacks of dystonia and are coupled to oscillations in face and hindlimb EMG activity. These transient oscillations and the associated cerebellar dysfunction provide a novel mechanism by which an ion channel disorder results in episodic motor dysfunction.",
keywords = "Autofluorescence, Cerebellum, Channelopathy, Dystonia, Episodic ataxia, Flavoprotein, Optical imaging, Oscillation, P/Q calcium channels, Tottering mouse",
author = "Gang Chen and Popa, {Laurentiu S} and Xinming Wang and Wangcai Gao and Justin Barnes and Claudia Hendrix and Hess, {Ellen J.} and Ebner, {Timothy J}",
year = "2009",
month = "6",
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T1 - Motor dysfunction in the tottering mouse is linked to cerebellar spontaneous low frequency oscillations revealed by flavoprotein autofluorescence optical imaging

AU - Chen, Gang

AU - Popa, Laurentiu S

AU - Wang, Xinming

AU - Gao, Wangcai

AU - Barnes, Justin

AU - Hendrix, Claudia

AU - Hess, Ellen J.

AU - Ebner, Timothy J

PY - 2009/6/1

Y1 - 2009/6/1

N2 - Flavoprotein autofluorescence optical imaging is developing into a powerful research tool to study neural activity, particularly in vivo. In this study we used this imaging technique to investigate the neuronal mechanism underlying the episodic movement disorder that is characteristic of the tottering (tg) mouse, a model of episodic ataxia type 2. Both EA2 and the tg mouse are caused by mutations in the gene encoding Ca v2.1 (P/Q-type) voltage-gated Ca 2+ channels. These mutations result in a reduction in P/Q Ca 2+ channel function. Both EA2 patients and tg mice have a characteristic phenotype consisting of transient motor attacks triggered by stress, caffeine or ethanol. The neural events underlying these episodes of dystonia are unknown. Flavoprotein autofluorescence optical imaging revealed spontaneous, transient, low frequency oscillations in the cerebellar cortex of the tg mouse. Lasting from 30 - 120 minutes, the oscillations originate in one area then spread to surrounding regions over 30 - 60 minutes. The oscillations are reduced by removing extracellular Ca 2+ and blocking Ca v 1.2/1.3 (L-type) Ca 2+ channels. The oscillations are not affected by blocking AMPA receptors or by electrical stimulation of the parallel fiber - Purkinje cell circuit, suggesting the oscillations are generated intrinsically in the cerebellar cortex. Conversely, L-type Ca 2+ agonists generate oscillations with similar properties. In the awake tg mouse, transcranial flavoprotein imaging revealed low frequency oscillations that are accentuated during caffeine induced attacks of dystonia. The oscillations increase during the attacks of dystonia and are coupled to oscillations in face and hindlimb EMG activity. These transient oscillations and the associated cerebellar dysfunction provide a novel mechanism by which an ion channel disorder results in episodic motor dysfunction.

AB - Flavoprotein autofluorescence optical imaging is developing into a powerful research tool to study neural activity, particularly in vivo. In this study we used this imaging technique to investigate the neuronal mechanism underlying the episodic movement disorder that is characteristic of the tottering (tg) mouse, a model of episodic ataxia type 2. Both EA2 and the tg mouse are caused by mutations in the gene encoding Ca v2.1 (P/Q-type) voltage-gated Ca 2+ channels. These mutations result in a reduction in P/Q Ca 2+ channel function. Both EA2 patients and tg mice have a characteristic phenotype consisting of transient motor attacks triggered by stress, caffeine or ethanol. The neural events underlying these episodes of dystonia are unknown. Flavoprotein autofluorescence optical imaging revealed spontaneous, transient, low frequency oscillations in the cerebellar cortex of the tg mouse. Lasting from 30 - 120 minutes, the oscillations originate in one area then spread to surrounding regions over 30 - 60 minutes. The oscillations are reduced by removing extracellular Ca 2+ and blocking Ca v 1.2/1.3 (L-type) Ca 2+ channels. The oscillations are not affected by blocking AMPA receptors or by electrical stimulation of the parallel fiber - Purkinje cell circuit, suggesting the oscillations are generated intrinsically in the cerebellar cortex. Conversely, L-type Ca 2+ agonists generate oscillations with similar properties. In the awake tg mouse, transcranial flavoprotein imaging revealed low frequency oscillations that are accentuated during caffeine induced attacks of dystonia. The oscillations increase during the attacks of dystonia and are coupled to oscillations in face and hindlimb EMG activity. These transient oscillations and the associated cerebellar dysfunction provide a novel mechanism by which an ion channel disorder results in episodic motor dysfunction.

KW - Autofluorescence

KW - Cerebellum

KW - Channelopathy

KW - Dystonia

KW - Episodic ataxia

KW - Flavoprotein

KW - Optical imaging

KW - Oscillation

KW - P/Q calcium channels

KW - Tottering mouse

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U2 - 10.1117/12.816656

DO - 10.1117/12.816656

M3 - Conference article

VL - 7180

JO - Progress in Biomedical Optics and Imaging - Proceedings of SPIE

JF - Progress in Biomedical Optics and Imaging - Proceedings of SPIE

SN - 1605-7422

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ER -