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1. Depolarization-induced suppression of inhibition (DSI) is a form of synaptic plasticity which involves a retrograde messenger. We have performed experiments in Purkinje cells of rat cerebellar slices to determine the nature of this messenger. 2. DSI is mimicked by 2-(2,3-dicarboxycyclopropyl)-glycine (DCG-IV), a specific agonist of group II metabotropic glutamate receptors (mGluRs). 3. DSI is reduced if transmitter release is inhibited by saturating doses of DCG-IV. 4. Both DSI and DCG-IV-induced inhibition are inhibited by L-2-amino-3-phosphonopropionic acid (L-AP3), a drug which interferes with several subtypes of mGluRs. 5. DSI is reduced if synaptic activity is enhanced by application of forskolin. 6. We propose that glutamate or a glutamate-like substance is the retrograde messenger implicated in DSI, and that the inhibition resulting from presynaptic glutamate binding is mediated by a decrease in the presynaptic concentration of cAMP.


Journal article


J Physiol

Publication Date



497 ( Pt 2)


531 - 537


2-Amino-5-phosphonovalerate, Alanine, Animals, Benzoates, Colforsin, Cyclopropanes, Electrophysiology, Excitatory Amino Acid Antagonists, Glutamic Acid, Glycine, Interneurons, Kinetics, Presynaptic Terminals, Purkinje Cells, Quinoxalines, Rats, Receptors, Metabotropic Glutamate, Synapses, Synaptic Transmission, Tetrodotoxin