On the mechanism of long-term potentiation induced by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) in rat hippocampal slices.
We have reported previously that transient application of a specific metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (ACPD) can induce a slow-onset form of long-term potentiation (LTP) of synaptic transmission in the CA1 region of rat hippocampal slices [Bortolotto Z. A. and Collingridge G. L. (1993) Neuropharmacology 32, 1-9]. Here we have investigated further the mechanisms involved in the induction and expression of ACPD-induced LTP. Unless otherwise stated, field excitatory postsynaptic potentials (EPSPs) were recorded in stratum radiatum in response to low frequency (0.033 Hz stimulation) of the Schaffer collateral-commissural pathway and 10 microM ACPD was added for 20 min to the perfusate. ACPD-induced LTP was still observed following blockade of GABAA receptor-mediated synaptic inhibition using picrotoxin (50 microM) and was not the result of a change in the presynaptic fibre volley. Intracellular recording from area CA1 revealed an increase in the size of the EPSP but no associated change in membrane potential or input resistance. However, ACPD-induced potentiation was never seen when intracellular electrodes contained the Ca(2+)-chelating agent 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA; 0.5 M). In area CA3, ACPD elicited a slow-onset LTP of the intracellularly recorded EPSP, evoked by stimulation of associational fibres. In contrast to area CA1, 10 microM ACPD depolarized CA3 neurones. Unlike certain other forms of tetanus- and chemically-induced potentiation, ACPD-induced LTP was not affected by the L-type Ca2+ channel antagonist nimodipine (50 microM). It was, however, prevented by delivering low frequency stimulation (900 shocks at 1 Hz) immediately following termination of the application of ACPD; an effect which was inhibited by the specific N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonopentanoate (AP5; 50 microM). ACPD failed to induce LTP of pharmacologically-isolated NMDA receptor-mediated EPSPs. The induction of ACPD-induced LTP was blocked by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), in a reversible manner. In slices in which area CA3 had been removed ACPD failed to induce LTP when applied alone or together with AMPA. However, a slow-onset form of LTP was induced, in slices lacking area CA3, when a tetanus (100 Hz, 1 sec) was delivered in the presence of ACPD and 50 microM AP5 (the latter applied to prevent conventional tetanus-induced LTP). ACPD-induced LTP was associated with a parallel increase in the sensitivity of CA1 neurones to AMPA. Considered together, these data suggest that ACPD-induced LTP is due to a direct increase in the AMPA receptor-mediated synaptic conductance and involves postsynaptic induction and expression mechanisms.
Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, U.K.
Z A
ZA
Bortolotto
G L
GL
Collingridge
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D017661:Receptors, Presynaptic / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D017661:Receptors, Presynaptic; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D009553:Nimodipine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid