Differential Roles of Apamin- and Charybdotoxin-Sensitive K+ Conductances in the Generation of Inferior Olive Rhythmicity In Vivo

The basic electrical rhythmicity of the olivocerebellar system was investigated in vivo using multiple electrode recordings of Purkinje cell (PC) complex spike (CS) activity. CSs demonstrate a 10 Hz rhythmicity, thought to result from the interaction of Ca2+ and Ca2+-dependent K+conductances present in inferior olivary (IO) neurons. To assess the roles of different K+ channels in generating this rhythmicity, intraolivary microinjections of charybdotoxin (CTX) and apamin were used. Both K+ channel blockers increased average CS spike-firing rates. However, apamin produced a tonic increase in firing with a decrement in the CS rhythmicity. In contrast, after CTX administration, highly rhythmic CS discharges were interleaved with silent periods, suggesting that apamin- and CTX-sensitive K+ channels have distinct rhythmogenic roles in IO neurons. CTX-sensitive channels seem to be functionally coupled to low threshold Ca2+ channels, whereas the apamin-sensitive channels relate to high threshold Ca2+channels. Blocking intraolivary GABAA receptors increases IO excitability and the spatial distribution of synchronized CS activity while disrupting its rostrocaudal banding pattern (Lang et al., 1996). The present experiments show that K+ channel blockers increase IO excitability without causing widespread synchronization of CS activity. Thus, changes in the IO excitability have relatively little effect in determining the spatial organization of CS synchrony. In contrast, the degree of CS rhythmicity seemed to influence the patterns of CS synchrony. Thus, after CTX, increased CS rhythmicity was associated with increased intraband synchrony and decreased interband synchrony, whereas apamin had the opposite effects on intra- and interband synchronization.

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