title: Activation of group I metabotropic glutamate receptors induces long-term depression at sensory synapses in superficial spinal dorsal horn.
abstract: Low-frequency stimulation of primary afferent Adelta-fibers can induce long-term depression of synaptic transmission in rat superficial spinal dorsal horn. Here, we have identified another form of long-term depression in superficial spinal dorsal horn neurons that is induced by specific group I but not group II metabotropic glutamate receptor (mGluR) agonists. Synaptic strength between Adelta-fibers and dorsal horn neurons was examined by intracellular recordings in a spinal cord-dorsal root slice preparation from young rat. In the presence of bicuculline and strychnine, bath application of (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid ((1S,3R)-ACPD) or the specific group I mGluR agonist (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) but not the specific group II mGluR agonist (2S,2'R,3'R)-2-(2', 3'-dicarboxycyclopropyl)glycine (DCG-IV) for 20 min produced an acute and a long-term depression of synaptic strength. Bath application of the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonovaleric acid did not affect these depressions by (1S,3R)-ACPD. After pre-incubation of slices with pertussis toxin, a G-protein inhibitor, (1S,3R)-ACPD still induced acute and long-term depressions. The phospholipase C inhibitor U73122 stereoselectively blocked the induction of long-term depression without affecting acute synaptic inhibition. This study demonstrates that, in the spinal cord, direct activation of group I mGluRs that are coupled to phospholipase C through pertussis toxin-insensitive G-proteins induces a long-term depression of synaptic strength. This may be relevant to the processing of sensory information in the spinal cord, including nociception.
authors.affiliation: Institute of Physiology and Pathophysiology, University of Heidelberg, 69120, Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: B
authors.initials: B
authors.lastname: Heinke
authors.forename: J
authors.initials: J
authors.lastname: Sandkühler
mesh_terms: D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003864:Depression, Chemical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000737:chemistry / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D019204:GTP-Binding Proteins / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects*; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013237:Stereoisomerism; D013569:Synapses / Q000187:drug effects*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D004963:Estrenes; D011760:Pyrrolidinones; D018094:Receptors, Metabotropic Glutamate; D010566:Virulence Factors, Bordetella; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins