L-2-AMINO-4-PHOSPHONOBUTANOIC ACID AND 1S,3R-1-AMINOCYCLOPENTANE-1,3-DICARBOXYLIC ACID REDUCE PAIRED-PULSE DEPRESSION RECORDED FROM MEDIAL PERFORANT PATH IN THE DENTATE GYRUS OF RAT HIPPOCAMPAL SLICES

The perforant path is the major excitatory cortical projection to the hippocampal dentate gyrus. Field potentials from the medial perforant path exhibit paired-pulse depression when evoked at interstimulus intervals of 40 to 800 msec. We found that an early component of paired-pulse depression recorded at interstimulus intervals of 40 to 1 00 msec from slices of rat hippocampus was reduced by L-2-amino-4-phosphonobutanoic acid (L-AP4) (20 muM) without a change in the size of the first field potential in the pair. Paired-pulse depression evoked at intervals of 200 to 800 msec was not reduced. 1S,3R-1-Aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), DL-2-amino-3-phosphonopropionic acid and carbachol also reduced paired-pulse depression in a manner similar to L-AP4. Picrotoxin, phaclofen, theophylline or atropine did not reduce paired-pulse depression. Furthermore, paired-pulse depression (40-100 msec) does not appear to involve glutamate uptake or N-methyl-D-aspartate receptors as L-alpha-aminoadipate did not alter paired-pulse depression and neither trans-L-pyrrolidine-2,4-dicarboxylate and L-alpha-aminoadipate nor D-2-amino-5-phosphonopropionic acid blocked the effect Of L-AP4 on paired-pulse depression. 4-Aminopyridine inhibits a potassium current that has a similar time course to the L-AP4-induced reduction of paired-pulse depression, however, paired-pulse depression was increased with exposure to 4-aminopyridine. These results indicate that the mechanism underlying paired-pulse depression consists of two components, the early component being reduced by L-AP4, 1S,3R-ACPD, DL-2-amino-3-phosphonopropionic acid and carbachol. These results also characterize an effect Of L-AP4 on synaptic activity that appears to be distinct from L-AP4-induced inhibition of glutamate release previously described in other pathways. L-AP4 and 1S,3R-ACPD may reduce paired-pulse depression by activating similar receptors or through similar intracellular signaling mechanisms.