Metabotropic glutamate receptors are required for the induction of long-term potentiation.
Recent observations have led to the suggestion that the metabotropic glutamate receptor may play a role in the induction or maintenance of long-term potentiation (LTP). However, experimental evidence supporting a role for this receptor in the induction of LTP is still inconclusive and controversial. Here we report that, in rat dorsolateral septal nucleus (DLSN) neurons, which have the highest density of metabotropic receptors and show functional responses, the induction of LTP is not blocked by the NMDA receptor antagonist 2-amino-5-phosphonovalerate, but is blocked by two putative metabotropic glutamate receptor antagonists, L-2-amino-3-phosphonopropionic acid and L-2-amino-4-phosphonobutyrate. Furthermore, superfusion of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, a selective metabotropic glutamate agonist, resulted in a long-lasting potentiation of synaptic transmission similar to that induced by tetanic stimuli. Our results demonstrated that activation of postsynaptic metabotropic receptors is both necessary and sufficient for the induction of LTP in the DLSN, and we suggest that such a mechanism may be important at other CNS synapses.
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
F
F
Zheng
J P
JP
Gallagher
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology*; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D016548:Prosencephalon / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000032:analysis / Q000502:physiology*; D013569:Synapses / Q000737:chemistry / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors
D000613:Aminobutyrates; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C000211:2-amino-3-phosphonopropionic acid; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004533:Egtazic Acid; D015763:2-Amino-5-phosphonovalerate; C012729:2-amino-4-phosphonobutyric acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000409:Alanine; D002118:Calcium