Amino acid neurotransmission between fimbria-fornix fibers and neurons in the lateral septum of the rat: a microiontophoretic study.

We investigated the nature of the excitatory amino acid and the type of amino acid receptor involved in the projection of fimbria-fornix (fi-fx) fibers on neurons in the lateral septal complex (LSC) of the rat. It appeared that neurons which were strongly orthodromically activated (SOA) by stimulation of fi-fx fibers were excited by glutamate (GLU) and aspartate (ASP) at much lower ejecting currents than neurons which were only weakly orthodromically excited. In addition, GLU was a stronger agent than ASP, particularly in SOA septal cells. Two amino acid antagonists tested, glutamic acid diethylester (GDEE) and 2-amino-5-phosphonovaleric acid (2-APV), selectively antagonized responses to the amino acid agonists quisqualate (QUIS) and N-methyl-D-aspartate (NMDA), respectively. They also depressed GLU- and ASP-induced responses, although in that case the antagonists frequently had to be expelled with currents higher than those needed to block QUIS- and NMDA-evoked excitations. Furthermore, GDEE frequently antagonized GLU-induced responses better than ASP-evoked excitations, whereas 2-APV often blocked responses to ASP more effectively than those to GLU. It was observed that GDEE, ejected with currents that blocked responses to QUIS reversibly, decreased the number of synaptic responses induced in SOA cells by fi-fx stimuli. Synaptically induced excitation in these neurons was consistently unaffected by 2-APV, even when the antagonist was expelled with high currents. According to these results, LSC neurons, in particular the SOA neurons, are more readily activated by GLU than by ASP. Monosynaptic excitations elicited in SOA septal cells by fi-fx stimuli appear to be predominantly if not exclusively mediated by QUIS receptors. There are indications that GLU-induced responses in the LSC neurons are presumably mediated by the QUIS receptors. From these data it may be inferred that GLU rather than ASP is the transmitter involved in the projection of fi-fx fibers on LSC neurons.