(1S,3R)-1-AMINOCYCLOPENTANE-1,3-DICARBOXYLIC ACID-INDUCED BURST FIRING IS MEDIATED BY A NATIVE PERTUSSIS-TOXIN-SENSITIVE METABOTROPIC RECEPTOR AT RAT DORSOLATERAL SEPTAL NUCLEUS NEURONS

We have reported previously that a selective metabotropic glutamate re ceptor agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S, 3R-ACPD), caused two primary postsynaptic membrane changes, namely, a slow membrane depolarization, and burst firing in rat dorsolateral sep tal nucleus neurons. In addition, (1S,3R)-1-aminocyclopentane-1,3-dica rboxylic acid also potentiates a slow afterdepolarization in rat dorso lateral septal nucleus neurons. We now report that, among all the post synaptic membrane changes induced by (1S,3R)-1-aminocyclopentane-1,3-d icarboxylic acid, only the burst firing was selectively blocked by per tussis toxin pretreatment. Thus, aminocyclopentane-1,3-dicarboxylic ac id induced burst firing was mediated by a metabotropic receptor couple d to a pertussis toxin-sensitive GTP-binding protein, while the other induced cellular reponses may be mediated by metabotropic glutamate re ceptors insensitive to pertussis toxin. We further characterized this receptor pharmacologically. This metabotropic receptor is activated by several metabotropic glutamate receptor agonists, but is insensitive to L-glutamate or L-aspartate. On the basis of its agonist activity pr ofile, particularly the ineffectiveness of glutamate as an agonist, we have tentatively assigned the name aminocyclopentane-1,3-dicarboxylic acid metabotropic receptor, to this native, pertussis toxin-sensitive metabotropic receptor in the dorsolateral septal nucleus. Furthermore , this receptor is coupled to protein kinase C, probably via a phospho lipase C independent pathway.