Non- N-methyl- d-aspartate receptors mediating synaptic transmission in the avian cochlear nucleus: Effects of kynurenic acid, dipicolinic acid and streptomycin

Abstract

We have examined the effects of a number of excitatory amino acid antagonists on transmission at the cochlear nerve-nucleus magnocellularis synapse in the chicken. Using an in vitro preparation and bath application of drugs, we studied the effects of kynurenic acid and several related substances, streptomycin and a selective N-methyl- d-aspartate receptor antagonist, dl-α-aminosuberate. The last compound had no effect on evoked transmission. Of the various kynurenic acid-related compounds tested, only kynurenic and dipicolinic acid selectively altered responses in nucleus magnocellularis. Quinolinic acid, a kynurenic acid analogue that is structurally akin to dipicolinic acid but which acts selectively at N-methyl- d-aspartate receptors, was without effect. The effect of kynurenic acid was solely inhibitory, completely blocking postsynaptic responses with a potency dependent on the frequency of nerve stimulation. No such frequency dependence was seen with dipicolinic acid although this compound also completely suppressed evoked responses. In addition dipicolinic acid potentiated postsynaptic responses at concentrations only slightly lower than those causing inhibition. Streptomycin inhibited responses in nucleus magnocellularis but this effect seems to result partially from the ability of the drug to inhibit presynaptic calcium influx. Our finding that selective antagonists of N-methyl- d-aspartate receptors were ineffective while antagonists of both receptor types, such as kynurenic and dipicolinic acids, inhibited evoked responses reinforces the conclusion that postsynaptic receptors mediating transmission at this synapse are of thenon- N-methyl- d-aspartate type[Nemeth et al. (1983) Neurosci. Lett. 40, 39–44]. However, differences in the effects of kynurenic and dipicolinic acids on evoked responses indicate that they do not have a single common mechanism of action. Our results with streptomycin, although possibly reflecting the involvement of quisqualate-preferring receptors in transmission, also indicate that the usefulness of this drug as a probe for that receptor subtype may be limited by its non-specific actions. Finally, our findings differ from those in the cat anteroventral cochlear nucleus, mammalian homologue of nucleus magnocellularis, where N-methyl- d-aspartate receptors appear to mediate transmission. This difference between otherwise very similar synapses in two different species suggests that selection of a particular receptor and/or transmitter is largely independent of other functional properties.