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• W2074317967 endingPage "5679" @default.
• W2074317967 startingPage "5664" @default.
• W2074317967 abstract "The Ca 2+ channelopathies caused by mutations of the CACNA1A gene that encodes the pore-forming subunit of the human Ca v 2.1 (P/Q-type) voltage-gated Ca 2+ channel include episodic ataxia type 2 (EA2). Although, in EA2 the emphasis has been on cerebellar dysfunction, patients also exhibit episodic, nonmotoric abnormalities involving the cerebral cortex. This study demonstrates episodic, low-frequency oscillations (LFOs) throughout the cerebral cortex of tottering ( tg / tg ) mice, a widely used model of EA2. Ranging between 0.035 and 0.11 Hz, the LFOs in tg / tg mice can spontaneously develop very high power, referred to as a high-power state. The LFOs in tg / tg mice are mediated in part by neuronal activity as tetrodotoxin decreases the oscillations and cortical neuron discharge contain the same low frequencies. The high-power state involves compensatory mechanisms because acutely decreasing P/Q-type Ca 2+ channel function in either wild-type (WT) or tg / tg mice does not induce the high-power state. In contrast, blocking l -type Ca 2+ channels, known to be upregulated in tg / tg mice, reduces the high-power state. Intriguingly, basal excitatory glutamatergic neurotransmission constrains the high-power state because blocking ionotropic or metabotropic glutamate receptors results in high-power LFOs in tg / tg but not WT mice. The high-power LFOs are decreased markedly by acetazolamide and 4-aminopyridine, the primary treatments for EA2, suggesting disease relevance. Together, these results demonstrate that the high-power LFOs in the tg / tg cerebral cortex represent a highly abnormal excitability state that may underlie noncerebellar symptoms that characterize CACNA1A mutations." @default.
• W2074317967 created "2016-06-24" @default.
• W2074317967 creator A5016058668 @default.
• W2074317967 creator A5025929177 @default.
• W2074317967 creator A5045067652 @default.
• W2074317967 creator A5057393168 @default.
• W2074317967 creator A5080137149 @default.
• W2074317967 date "2015-04-08" @default.
• W2074317967 modified "2023-09-23" @default.
• W2074317967 title "Abnormal Excitability and Episodic Low-Frequency Oscillations in the Cerebral Cortex of the<i>tottering</i>Mouse" @default.
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