Excitatory amino acid-mediated modulation of synaptic transmission in rat hippocampal slices
The whole-cell patch-clamp technique was established in the laboratory in order to investigate the modulation of excitatory amino acid-mediated synaptic transmission in the rat hippocampal slice. Following the successful development of the technique the basic properties of excitatory amino acid-mediated synaptic transmission in the CA3-CA1 pathway were studied. Stimulation of the SCCFs (Schaffer collateral-commissural fibres) under conditions in which the inhibitory transmission was blocked resulted in a compound EPSC (excitatory postsynaptic current) mediated by AMPA (-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors. Application of a brief high-frequency stimulus to the SCCFs resulted in a long-lasting potentiation of the EPSC. Various compounds were applied to the slice to establish whether tetanus-induced potentiation could be mimicked pharmacologically. No potentiation was observed with perfusion of the ionotropic glutamate-receptor agonists L-glutamate, NMDA or AMPA, the latter two producing a transient depression of the EPSC. Following this a series of experiments were performed that investigated the consequences of mGluR (metabotropic glutamate receptor) activation. Perfusion with the selective agonist 1S,3R-ACPD ((1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid) resulted in a small depression of both the compound EPSC and the isolated NMDA receptor-mediated EPSC. In the presence of AA (arachidonic acid (10M)), 1S,3R-ACPD produced a slight potentiation of the response that was not blocked by the NMDA receptor antagonist D-AP5 (D-(-)-2-amino-5-phosphonopentanoic acid). The co-application of 1S,3R-ACPD and NMDA also produced a slight enhancement of the EPSC, as did AA when applied alone. These findings are consistent with an involvement of mGluRs in the induction of LTP, when activated in the presence of AA.