MULTIPHASIC RESPONSES OF CEREBELLAR PURKINJE-CELLS TO 1S,3R-ACPD - ANIN-VIVO STUDY

The effects of iontophoretically applied (1S,3R)-1-aminocyclopentane-1 ,3-dicarboxylic acid (1S,3R-ACPD), an agonist of metabotropic glutamat e receptors, were examined in rat cerebellar Purkinje cells in vivo. M ultibarrel electrodes were used for extracellular recordings of sponta neous single unit discharges and iontophoretic ejection of 1S,3R-ACPD. The. effect of 1S,3R-ACPD depended on both the strength and the durat ion of the iontophoretic current: Application of the agonist with ejec tion currents at or slightly above the response threshold for up to 60 s resulted in an increased rate of action potential firing. With larg er ejection currents of the same duration the initial increase in acti vity was followed by a depression and eventually a cessation of activi ty. In the transition phase between low frequency firing and firing ar rest, Purkinje cells generated almost exclusively complex spikes. When the drug application was continued for longer durations (1-10 min) th e initial response was followed by a characteristic cyclic firing patt ern. These cycles consisted of alternating phases of mainly simple spi ke activity, predominantly complex spike activity and silent intervals . At the end of drug applications using large ejection currents, a pro longed period (on average 66 s) with almost no spiking activity was ob served. This period ended with an abrupt onset of simple spike firing. These findings point to an important function of cerebellar metabotro pic glutamate receptors in the regulation of Purkinje cell activity.