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

Abstract

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 Ca 2ϩ and Ca 2ϩ -dependent K ϩ conductances present in inferior olivary (IO) neurons. To assess the roles of different K ϩ channels in generating this rhythmicity, intraolivary microinjections of charybdotoxin (CTX) and apamin were used. Both K ϩ 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 ϩ channels have distinct rhythmogenic roles in IO neurons. CTX-sensitive channels seem to be functionally coupled to low threshold Ca 2ϩ channels, whereas the apamin-sensitive channels relate to high threshold Ca 2ϩ channels.Blocking intraolivary GABA A 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 ϩ 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.

Microglial Ca2+-Activated K+Channels Are Possible Molecular Targets for the Analgesic Effects ofS-Ketamine on Neuropathic Pain

“…In in vivo studies, BK channels are inhibited by ChTX (1-4 ng) (Lang et al, 1997;Paton et al, 2001), resulting in enhancement of the neuronal excitability. Therefore, intrathecal ChTX administration was expected to cause an increase in neuronal excitability and enhancement of tactile allodynia.…”

In vivo analysis of Purkinje cell firing properties during postnatal mouse development

“…To derive the rhythm index, autocorrelograms for simple spikes were first plotted in Spike2 for each Purkinje cell, with a width of 1.0 s, an offset of 0.5 s, and a bin size of 5 ms. Numerical values of the plot were then exported to Excel, and the rhythm index was calculated using previously published equations (Lang et al 1997;Sugihara et al 1995) that were integrated into our custom Excel macros. First, the baseline level (average bin count) was calculated using the formula: baseline ϭ (total spike number) 2 (recording time/bin width) Random fluctuation about the baseline bin height was measured as the SD of spike counts per bin at time lags of Ϫ400 to Ϫ500 ms and 400 to 500 ms.…”

Functional circuitry involved in the regulation of whisker movements

“…It is possible that the red nucleus is involved in relaying inputs from the olivocerebellar system to wFMNs (Welsh et al, 1995). This is of interest because the characteristic frequency of rhythmic activity in the olivocerebellar system is similar to the frequency of rhythmic whisking (see, e.g., Lang et al, 1997). However, inactivation of the inferior olive does not affect exploratory whisker movements (Semba and Komisaruk, 1984), so this rhythmic activity may not be causally related to these movements.…”