SUMMARY1. The effects of excitatory amino acids and some antagonists applied by ionophoresis to stratum radiatum in the CAL region of rat hippocampal slices were examined on the locally recorded field e.p.s.p. evoked by stimulation of the Schaffer collateral-commissural projection.2. L-glutamate, L-aspartate and the more potent and selective excitatory amino acids quisqualate, kainate and N-methyl-DL-aspartate (NMA) depressed the e.p.s.p., presumably through depolarization and/or a change in membrane conductance.3. The depression induced by kainate considerably outlasted the period of ejection whereas NMA depressions were rapidly reversible and were often followed by a potentiation of the e.p.s.p. In higher doses NMA also depressed the presynaptic fibre volley. The possible involvement of these effects in neurotoxicity and synaptic plasticity is raised.4. The selective NMA antagonist, DL-2-amino-5-phosphonovalerate (APV) applied in doses which abolished responses to NMA, had no effect on the e.p.s.p. but prevented long term potentiation (l.t.p.) of synaptic transmission evoked by high frequency stimulation ofthe Schaffer collateral-commissural pathway. Other antagonists which had little or no effect on normal synaptic transmission included D-a-aminoadipate (DAA), the optical isomers of 2-amino-4-phosphonobutyrate (APB) and L-glutamate diethylester (GDEE).5. In contrast, y-D-glutamylglycine (DGG), applied in amounts which affected quisqualate and kainate actions as well as those of NMA, was an effective synaptic antagonist whilst having no effect on the presynaptic fibre volley.6. These results indicate that the synaptic receptor in the Schaffer collateralcommissural pathway may be of the kainate or quisqualate type. Although NMA receptors do not appear to be involved in normal synaptic transmission in this pathway they may play a role in synaptic plasticity. The interaction of L-glutamate and L-aspartate with these receptors is discussed.

SUMMARY1. The effects ofthe ionophoretic application of a number ofexcitatory amino acids and antagonists to the dendrites of CAI neurones of rat hippocampal slices maintained in vitro were examined. Cells were excited by N-methyl-DL-aspartate (NMA), kainate, quisqualate, L-aspartate and L-glutamate; NMA was unique in causing cells to fire in bursts of repetitive discharges in contrast to the sustained firing seen with the other compounds.2. D-(-)-a-aminoadipate (DAA) and (±)-2-amino-5-phosphonovalerate (APV) were selective NMA antagonists, the latter appearing to be the more potent; in addition both compounds potentiated the responses to kainate and quisqualate. L-glutamate excitations were affected less by APV than were those of L-aspartate. The antagonist properties of APV appeared to reside with the D-(-)-isomer.3. y-D-glutamylglycine (DGG) in low ionophoretic doses inhibited NMA-, kainateand aspartate-induced cell firing but at higher doses the quisqualate and glutamate responses were also decreased.4. Kainate and NMA responses were blocked by D-(-)-2-amino-4-phosphonobutyrate (D-APB) which also had some action against the excitatory effects of L-aspartate. L-APB had no antagonistic effects, but often produced potentiation of amino acid excitations or was itself an excitant.5. The effects of NMA and those of kainate and quisqualate were blocked by (± )-cis-2,3-piperidine dicarboxylate (PDA), but this compound itself had a direct excitatory effect. L-glutamate diethylester (GDEE) did not show specific antagonism of any amino acid excitations.6. DGG and APV did not affect ACh excitations and these selective antagonists should be of value in studying the involvement of the excitatory amino acids in synaptic transmission in the hippocampus. Because they are less potent and/or have complicating direct effects PDA, GDEE, D-and L-APB may be less useful in this regard.

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SUMMARY1. Records of field potentials and of the firing patterns of single neurones evoked by stimulation of the fimbria and fornix have been obtained from the septal nuclei of the rat.2. Fimbrial stimulation caused orthodromic activation of lateral septal neurones which was followed by a lengthy inhibition. In the medial septum such stimulation could elicit an antidromic response; but inhibition whose duration depended upon whether the neurones were firing irregularly or in synchronized bursts was obtained without prior activation.3. Stimulation of the medial septum evoked an antidromic response in the lateral septal neurones, which was followed by inhibition.4. For all of these inhibitory phenomena, bursts of action potentials of small amplitude and correlated with the start of the inhibitory periods were observed, and are believed to indicate the firing of inhibitory interneurones.5. Stimulation of the fornix caused excitation of medial septal neurones but was without effect on those in the lateral septum.6. A scheme is proposed in which the direct inhibition of medial septal neurones from the fimbria is suggested to act as a 'reset' mechanism, while the phasic input from lateral septum resulting from the recurrent inhibitory pathways regulates the frequency of bursting in the medial septum.