title: Agonists at metabotropic glutamate receptors presynaptically inhibit EPSCs in neonatal rat hippocampus.
abstract: 1. The effects of metabotropic glutamate receptor agonists on excitatory synaptic transmission in the CA1 region of rat hippocampal slices (11-30 days) were studied using extracellular and whole-cell patch-clamp recording techniques. 2. Trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD; 25-100 microM) reversibly depressed excitatory postsynaptic currents (EPSCs) without affecting presynaptic fibre excitability or EPSC reversal potential. 3. Ibotenate (25 microM) or L-glutamate (250 microM), in the presence of the N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovaleric acid (APV, 50-75 microM), depressed the EPSC amplitude while inducing no detectable inward current. L-2-Amino-4-phosphonobutyrate (L-AP4, 25-100 microM), the phosphonic derivative of glutamate, also depressed EPSC amplitude and caused no detectable inward current. 4. The NMDA receptor-mediated component of the EPSC recorded in the presence of the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20-30 microM) was depressed by trans-ACPD, L-AP4, or quisqualate (1-2 microM). 5. The response to ionophoretic application of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) was unaffected by trans-ACPD or L-AP4 although the simultaneously recorded EPSC was strongly depressed. In addition, paired-pulse facilitation (50-75 ms interstimulus interval) was reversibly enhanced by trans-ACPD or L-AP4. These results indicate that the depression of synaptic transmission likely was mediated by a presynaptic 'autoreceptor'. 6. The effects of trans-ACPD or L-AP4 on synaptic transmission decreased significantly over ages 12-30 days and were minimal in adult (greater than 80 days) slices. 7. The depression of synaptic transmission caused by trans-ACPD or L-AP4 was not altered following the induction of long-term potentiation (LTP). 8. The results indicate that metabotropic glutamate receptor agonists suppress excitatory synaptic transmission in CA1 pyramidal cells by an action at a presynaptic site. This effect is developmentally regulated and is maximally expressed during the first postnatal month.
authors.affiliation: Department of Psychiatry, University of California, San Francisco 94143.
authors.forename: A
authors.initials: A
authors.lastname: Baskys
authors.forename: R C
authors.initials: RC
authors.lastname: Malenka
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission
chemical_list: D000613:Aminobutyrates; D009498:Neurotoxins; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C012729:2-amino-4-phosphonobutyric acid