Cerebellar stellate cells are GABAergic interneurons located in the molecular layer. They are inhibited by other stellate cells and excited by granule cells. It has been shown that granule cells fire with high frequency upon whisker stimulation (Chadderton et al., 2004). Here, we activated granule cells extracellularly by such a train of stimuli in mouse cerebellar slices and examined the effects on GABAergic transmission between two stellate cells in whole-cell paired recordings. 30 stimuli at 50 Hz reduced the peak amplitude of IPSCs evoked by brief depolarization of the presynaptic cell by 28.0±4.7% (n = 8). The concomitant increases in failure rate, paired-pulse ratio and decrease in 1/CV2 indicated presynaptic mechanism(s) which could be induced at P14 but not at P21. The reduction of the eIPSCs was prevented by the AMPAR antagonist GYKI-53655 (50 mM) but not by NMDAR or mGluR blockers. Consistently, enforced AMPAR desensitization decreased the effect on eIPSCs and inhibition of AMPAR desensitization restored the maximal effect. We found no involvement of cannabinoid but of GABAB receptors, since antagonizing the receptors (CGP-55845; 500 nM) or blocking G proteins in the presynaptic cell via GDPbetaS generated a smaller eIPSC reduction. Thus, endogenous glutamate modulates GABA release from stellate cells involving GABAB receptors, likely activated by GABA released from surrounding cells, but the main modulators are AMPARs at pre- and/or postsynaptic sites. Supported by DFG 1064/6-2