Faculty Bibliography

We have previously shown that selective activation of group I metabotropic glutamate receptors (mGluRs) results in long-lasting enhancement of synchronized network activity in the hippocampal slice. Data herein suggest that activation of group I mGluRs need not result in this potentially epileptogenic effect. (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (ACPD), a nonselective mGluR agonist, elicits ictaform bursts identical in appearance to those induced by selective agonists, but ACPD-induced bursts do not persist following removal of the agent. Like the bursts induced by selective agonist, the ACPD bursts are blocked with group I mGluR antagonists and are not dependent on activation of either N-methyl-D-aspartate (NMDA) receptors or protein kinase C. However, they differ from the persistent bursts in that they do not require active protein synthesis and they are not suppressed with L-cysteine sulfinic acid, an agonist at a phospholipase D-coupled metabotropic receptor. These novel findings provide evidence that group I mGluR-induced epileptogenesis may be preventable.

Selective activation of group I metabotropic glutamate receptors (mGluRs) with (S)-3,5-dihydroxyphenylglycine (DHPG) in guinea pig hippocampal slices converts 275- to 475-ms picrotoxin-induced interictal bursts into persistent seizure-length discharges typically over 1 s in duration. Here we report that l-cysteine sulfinic acid (CSA), a sulfur-containing amino acid, prevented the induction of this persistent group I mGluR-mediated epileptiform burst prolongation. However, CSA had no effect on baseline interictal bursting activity and failed to suppress the expression of the group I mGluR-induced persistent prolonged bursts once they were fully induced. (2R,1'S,2'R,3'S)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-13), a selective antagonist at the phospholipase D (PLD)-coupled mGluR, had no effect of its own on DHPG-induced burst prolongation; however, CSA applied in the presence of PCCG-13 could no longer fully block the burst prolongation induced by DHPG, suggesting that CSA's antiepileptogenic effect is mediated by agonist action at this PLD-coupled receptor. These data parallel our previous data revealing that protein synthesis inhibitors prevent induction but not expression of group I mGluR-mediated persistent seizure-length discharges. Hence, PLD activation with CSA may prevent the synthesis of a protein critical for the induction of group I mGluR-mediated epileptogenesis.

Possible hemifield differences in texture segregation were investigated for both simple (Fourier, linear) and complex (non-Fourier, second-order) texture channels. There was only a very small lower-field advantage for texture segregation, consistent with the notion that the major processing in texture segregation is quite low level, perhaps V1. Complex-channel tasks do not show larger hemifield asymmetries than do simple-channel tasks, which suggests that the processes in complex texture channels are not higher level than those in simple.