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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.
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