The influence of gliotransmitter release from astrocytes on synaptic plasticity in the hippocampus remains unclear. Hippocampal astrocytes express two vesicular SNARE proteins, synaptobrevin II (SYB2) and cellubrevin (CEB), which are located on glutamatergic vesicles and neuropeptide-Y (NPY)-containing vesicles, respectively. Working with hippocampal cell culture and acute brain slices and comparing responses from mice lacking either SYB2, CEB or both, the authors show that whereas CEB-dependent NPY release from astrocytes decreases fast glutamatergic neurotransmission, SYB2-dependent glutamate release from astrocytes promotes such neurotransmission.