METABOTROPIC GLUTAMATE RECEPTOR -MEDIATED CURRENTS AT THE CLIMBING FIBER TO PURKINJE CELL SYNAPSE

Andjus P.R.(1,2), Bajić, A.(2), Zhu L.(1) & Strata P.(1)

1) Dept Neurosci., Univ. of Turin, Italy; 2) Dept Physiol. & Biochem., Sch. of Biology, Univ. of Belgrade, Serbia & Montenegro

Different forms of synaptic plasticity in the cerebellum expressed at the synapses onto Purkinje cells (PCs) are mediated by membrane metabotropic glutamate receptors (mGluRs). There are three main mGluR groups with a total of 8 subtypes. At parallel fiber (PF) to PC synapses activation of mGluRs gives rise to a well known slow synaptic current inhibited by antagonists of mGluR1 (group I). Although mGluRs are also found at climbing fiber (CF) to PC synapses the distribution of their types is not well known. Only recently an mGluR1(alfa)-mediated postsynaptic current was demonstrated at the CF-PC synapse (Dzubay & Otis, Neuron 36, 1159, 2002). Using whole cell patch-clamp recordings from PCs in rat cerebellar slices with ionotropic receptors blocked and impaired glutamate uptake we demonstrate a more complex pharmacology of a current obtained by single or train CF stimulation. The mGluR1 specific antagonist CPCCOEt in a group of cells suppressed this response but in a similar number of other cells induced a potentiating effect. It was noted that the potentiating effect of CPCCOEt is more frequent in animals above 35 days old. The antagonist of mGluR groups II and III, MSPG, additionally suppressed the current. Specific antagonists of both types II & III, LY341495 and MSOP, respectively, each inhibited mGluR currents. The effect of CPCCOEt was checked by measuring the paired-pulse depression of the CF EPSC, which was not changed with the antagonist, thus excluding a presynaptic effect. A 25% rise in amplitude with a prolongation of the decay time of CF EPSCs underlined a postsynaptic effect of CPCCOEt. However, the amplitude was not significantly affected in low Ca2+. Thus, mGluR1 gives rise to a slow postsynaptic current, but also regulates other presumably mGluR-dependent currents via second messenger molecules and Ca2+. In fact, the additional electrophysiological role of mGluR II & III was also underlined.

Email: pandjus@bf.bio.bg.ac.yu

Address: Dept for Physiology & Biochemistry, School of Biology; University of Belgrade, POB 52; 11001 Belgrade; Serbia & Montenegro