Hunter Jackson

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

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-alpha-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 the non-N-methyl-D-aspartate type [Nemeth et al. (1983) Neurosci. Lett. 40, 39-44].(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacological evidence for synaptic transmission mediated by non-n-methyl-d-aspartate receptors in the avian cochlear nucleus ☆

The hypothesis that synaptic transmission between the auditory nerve and the cochlear nucleus is mediated by an excitatory amino acid acting through N-methyl-D-aspartate (NMDA) receptors was examined in an in vitro preparation of the chicken brainstem. The ability of various bath-applied excitatory amino acid receptor antagonists to inhibit synaptically-evoked responses was assessed by recording field potentials from nucleus magnocellularis (NM) following electrical stimulation of the cochlear nerve. Antagonists that selectively block responses mediated by NMDA receptors, such as D-alpha-aminoadipate and 2-amino-5-phosphonovalerate, were without effect on evoked transmission in NM. In contrast, antagonists that additionally act on non-NMDA receptors, such as cis-2,3-piperidine dicarboxylate and gamma-D-glutamylglycine, reversibly suppressed transmission. The results indicate that (1) transmission in the chicken auditory system is mediated by non-NMDA receptors, and (2) a substance(s) chemically akin to aspartate and glutamate may be the transmitter used by the auditory nerve in NM.

Evidence for the involvement of kainate receptors in synaptic transmission in the avian cochlear nucleus

Previous studies using various excitatory amino acid antagonists have shown that synaptic transmission between the auditory nerve and the cochlear nucleus of chickens (nuc. magnocellularis; NM) is mediated by non-N-methyl-D-aspartate (non-NMDA) receptors. In the present study we have attempted to define the subclass of non-NMDA receptor in the NM by examining the effects of various excitatory amino acid agonists on synaptically evoked field potentials in an in vitro preparation of the chicken brain stem. Both quisqualate and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), whose actions operationally define the quisqualate receptor class, caused variable and weak depression of evoked responses in the NM, as did L-glutamate. Kainic acid, on the other hand, completely blocked postsynaptic responses at micromolar concentrations. We conclude that kainate-preferring non-NMDA receptors play a predominant role in mediating transmission in the NM.

Axon-target cell interactions in the developing auditory system.

Publisher Summary A number of significant developmental interactions between axons and their targets have been identified: for example, the role of afferent axons in shaping dendritic trees has been most clearly revealed for the Purkinje and basket/stellate neurons of the cerebellum, and the influence of target cells on neuronal survival has been studied most extensively in the chick spinal cord. Developmental regulation of the number of afferent axons converging on a target neuron has been most frequently examined in the peripheral nervous system (PNS), and the contributions of sensory experience to brain development have largely been revealed by work on the visual system of the cat. To obtain a more comprehensive view of these processes and their interrelationships, this chapter examines a variety of interactions between axons and their targets during the early life of certain auditory neurons in the avian brain stem. The striking structural and functional specializations of brain stem auditory neurons make them attractive subjects for studies of cellular interactions during the development of the central nervous system (CNS). The developing brain stem auditory nuclei of the chick embryo, in particular, are remarkable for the relative simplicity of their organization and their accessibility to the experimenter. The chapter presents the results of experimental studies involving the avian auditory system and summarizes recent work on its normal organization and development.

Anticonvulsant action of an arylamine-containing fraction from Agelenopsis spider venom.

A low molecular weight fraction (AG2) containing arylamine compounds has been isolated from venom of the spider Agelenopsis aperta. When administered intravenously or intracerebroventricularly, AG2 produces dose-dependent suppression of behavioral convulsions induced in rats by kainic acid, picrotoxin, or bicuculline. The low molecular weight compounds in spider venoms may provide novel tools for anticonvulsant research and therapy.

Chapter 30. Polyamine Spider Toxins: Unique Pharmacological Tools

Publisher Summary The polyamine toxins, obtained from the venom of a variety of orb-weaver spiders are rapidly emerging as unique tools for understanding excitatory amino acid (EM) transmission and related pharmacology or physiology. In this chapter, the chemistry and pharmacology of Araneidae polyamine spider venom toxins is reviewed and a brief discussion of the venom from the funnel-web spider is also included. The chemistry involved in the preparation of many of the naturally occurring polyamines has been discussed in the chapter. Polyamine spider venoms have highly polar hydroxyaryl and amino acid residues. Interest in the polyamine spider toxins is a result of the observation that these molecules affect those synapses, at which an excitatory amino acid (EAA) is the neurotransmitter. Compounds that affect EAA function, particularly those that antagonize the action of such transmitters, are therefore of considerable agricultural (insect control) and therapeutic interest. Blockade of neuromuscular transmission in invertebrates by polyamin spider toxins reveals their glutamate antagonist activity. Polyamine spider venoms also act on glutaminergic synapses in vertebrate systems. Partially purified JSTX blocks the responses of CA1 pyramidal neurons in rat hippocampus both to stimulation of the appropriate afferent neurons and to direct the application of glutamate. A variety of venoms have been screened for their ability to block synaptic transmission at glutaminergic synapses in the chick cochlear nucleus. A number of toxins from the funnel-web spider Agelenopsis aperta paralyze insects. These toxins contain low molecular weight acylpolyamine constituents, at least six amino acid residue peptides, and several larger polypeptides. Two classes of toxins from Agelenopsis aperta venom that block the transmission in the chick cochlear nucleus assay have also been discussed in the chapter. The results of these studies suggest that considerable structural and functional diversity exists within the polyamine toxin class and that these compounds differ significantly from previously-known classes of EAA and calcium antagonists.