Long-lasting modulation of synaptic input to Purkinje neurons by Bergmann glia stimulation in rat brain slices

Information processing in the nervous system is achieved primarily at chemical synapses between neurons. Recent evidence suggests that glia-neuron interactions contribute in multiple ways to the synaptic process. In the present study we used the frequency of spontaneous postsynaptic currents (sPSC) in Purkinje neurons in acute cerebellar brain slices from juvenile rats (13-19 days old) as a measure of synaptic activity. Following 50 depolarizing pulses to an adjacent Bergmann glial cell (50 mV; duration 0.5 s; 1 Hz) the sPSC frequency of the Purkinje neuron was reduced to 65 +/- 7 % of control values within 10 min after glial stimulation and remained depressed for at least 40 min. Depolarizing pulses to 0 mV had a comparable effect (70 +/- 5 % of control). The frequency of miniature PSCs, as recorded in 300 nM TTX, was not modulated after glial stimulation. Blockade of ionotropic glutamate receptors (iGluRs) with kynurenic acid (1 mM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5 microM) suppressed the reduction of neuronal activity induced by glial depolarization, whereas the glial modulation of synaptic activity was not inhibited by a block of N-methyl-D-aspartate iGluRs, metabotropic glutamate receptors, cannabinoid receptors or GABA(B) receptors. Fluorometric measurements of the intraglial Ca(2+) concentration revealed no glial Ca(2+) transients during the depolarization series, and glial cell stimulation reduced the neuronal sPSC frequency even after loading the glial cell with 20 mM of the Ca(2+) chelator BAPTA. Our results indicate a glia-induced long-lasting depression of neuronal communication mediated by iGluRs.