Abstract
In recent years, it has become clear that, in addition to conventional anterograde transmission, signaling in neural circuits can occur in a retrograde manner. This suggests the additional possibility that postsynaptic release of neurotransmitter might be able to act in an autocrine fashion. Here, we show that brief depolarization of a cerebellar Purkinje cell triggers a slow inward current. This depolarization-induced slow current (DISC) is attenuated by antagonists of mGluR1 or TRP channels. DISC is eliminated by a mixture of voltage-sensitive Ca2+ channel blockers and is mimicked by a brief climbing fiber burst. DISC is attenuated by an inhibitor of vesicular glutamate transporters or of vesicular fusion. These data suggest that Ca2+-dependent postsynaptic fusion of glutamate-loaded vesicles evokes a slow inward current produced by activation of postsynaptic mGluR1, thereby constituting a useful form of feedback regulation.