Share Email Print

Proceedings Paper

Motor dysfunction in the tottering mouse is linked to cerebellar spontaneous low frequency oscillations revealed by flavoprotein autofluorescence optical imaging
Author(s): Gang Chen; Laurentiu S Popa; Xinming Wang; Wangcai Gao; Justin Barnes; Claudia M. Hendrix; Ellen J. Hess; Timothy J. Ebner
Format Member Price Non-Member Price
PDF $14.40 $18.00

Paper 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 Cav2.1 (P/Q-type) voltage-gated Ca2+ channels. These mutations result in a reduction in P/Q Ca2+ 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 Ca2+ and blocking Cav 1.2/1.3 (L-type) Ca2+ 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 Ca2+ 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.

Paper Details

Date Published: 23 February 2009
PDF: 11 pages
Proc. SPIE 7180, Photons and Neurons, 71800C (23 February 2009); doi: 10.1117/12.816656
Show Author Affiliations
Gang Chen, Univ. of Minnesota (United States)
Laurentiu S Popa, Univ. of Minnesota (United States)
Xinming Wang, Univ. of Minnesota (United States)
Wangcai Gao, Univ. of Minnesota (United States)
Justin Barnes, Univ. of Minnesota (United States)
Claudia M. Hendrix, Univ. of Minnesota (United States)
Ellen J. Hess, Emory Univ. (United States)
Timothy J. Ebner, Univ. of Minnesota (United States)

Published in SPIE Proceedings Vol. 7180:
Photons and Neurons
Anita Mahadevan-Jansen; E. Duco Jansen, Editor(s)

© SPIE. Terms of Use
Back to Top