1S,3R-ACPD-PREFERRING INWARD CURRENT IN RAT DORSOLATERAL SEPTAL NEURONS IS MEDIATED BY A NOVEL EXCITATORY AMINO-ACID RECEPTOR

Metabotropic glutamate receptors (mGluRs) form a receptor family that consists of diverse receptor subtypes; now, numbering 8-exclusive of s plice variants. (1S,3R)-1-aminocycropentane-1,3-dicarboxylic acid (1S, 3R-ACPD) has been suggested to be a selective agonist for the mCluRs. We have recently reported that, in rat dorsolateral septal nucleus (DL SN) neurones, a 1S,3R-ACPD-preferring inward current (ACPD(i)) persist s in pertussis toxin-treated rats. We now report that this ACPD(i)-cur rent: (1) persists in DLSN neurones dialyzed with a stable analog of G TP, namely, GTP gamma S; (2) exhibits a negative slope region with inw ard rectification in its I-V relationship; (3) persists in neurones su perfused with tetrodotoxin or low calcium solutions; (4) is dependent upon both sodium and calcium ions; and (5) is independent of a reducti on in temperature. Furthermore, pharmacological data suggest that this current may be activated by a unique type of excitatory amino acid (E AA) receptor, i.e. a receptor which prefers ''metabotropic'' EAA agoni sts and is insensitive to AP5 or CNQX. Activation by ACPD of inward cu rrents associated with a conductance increase have also been reported at cultured mouse cerebellar Purkinje neurones; in slices of rat hippo campal CAI neurones and slice cultures of hippocampal CA3 neurones. We suggest that this ACPD(i) current may play an important role within t he CNS in the induction of long-term potentiation and other neurologic al processes; processes attributed previously to currents associated w ith NMDA receptor activation.