Glutamate as a candidate retrograde messenger at interneurone-Purkinje cell synapses of rat cerebellum.
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.
Glitsch
M
M
Arbeitsgruppe Zelluläre Neurobiologie, Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Germany.
Llano
I
I
Marty
A
A
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007395:Interneurons / Q000737:chemistry / Q000502:physiology*; D007700:Kinetics; D017729:Presynaptic Terminals / Q000737:chemistry / Q000502:physiology; D011689:Purkinje Cells / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D013569:Synapses / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D001565:Benzoates; D003521:Cyclopropanes; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018094:Receptors, Metabotropic Glutamate; C000211:2-amino-3-phosphonopropionic acid; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C079694:alpha-methyl-4-carboxyphenylglycine; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D005576:Colforsin; D018698:Glutamic Acid; D013779:Tetrodotoxin; D015763:2-Amino-5-phosphonovalerate; D000409:Alanine; D005998:Glycine