ABSTRACT
Intracellular recordings from neurons in brain slice preparations of the mouse ventral cochlear nucleus (VCN) were used to examine the actions of excitatory amino acid agonists and antagonists. Synaptic responses to electrical stimulation of the auditory nerve root were partially blocked by kynurenic acid, an antagonist that is specific for glutamate receptors. The antagonists specific for N-methyl-D-aspartate (NMDA), DL-2-amino-5-phosphonovalerate (APV) and Mg2+, did not affect the response, arguing against a role for NMDA receptors at the VIIIth nerve synapse. To test postsynaptic sensitivity to excitatory amino acid agonists, responses to bath applications were measured in VCN neurons while synaptic transmission was blocked by the removal of Ca2+ from the bath or by the addition of tetrodotoxin. Neurons in the VCN were 500-1000 times more sensitive to kainate than to glutamate or aspartate. In the absence of Mg2+, they were also sensitive to NMDA. The responses to kainate and glutamate were increased by the removal of calcium from the bath. These results imply that VCN neurons have both kainate and NMDA receptors and that synaptic transmission between auditory nerve fibers and neurons in the cochlear nuclear complex could be mediated by a substance related to kainate.
Subject(s)
Kainic Acid/physiology , Receptors, Neurotransmitter/physiology , Vestibulocochlear Nerve/physiology , Action Potentials/drug effects , Animals , Aspartic Acid/analogs & derivatives , Aspartic Acid/pharmacology , Electric Stimulation , Glutamates/pharmacology , Glutamic Acid , In Vitro Techniques , Kainic Acid/pharmacology , Mice , Mice, Inbred CBA , N-Methylaspartate , Receptors, Glutamate , Receptors, Neurotransmitter/drug effects , Vestibulocochlear Nerve/metabolismABSTRACT
Results obtained in a study using an in vivo microdialysis technique show that dopamine is detected in perfusates collected from the frontoparietal (sensorimotor) cortex of control rats (dopamine = 0.7 +/- 0.2 nM, n = 10) or of rats with cortical lesions produced by the neurotoxin kainic acid (0.9 +/- 0.2 nM, n = 4). However, cortical dopamine levels were strongly reduced (0.07 +/- 0.06 nM, n = 4) following deafferentation induced by mesencephalic 6-hydroxydopamine injection. Dopamine levels, but not its metabolites could be increased by local KCl application, supporting the idea that extracellular dopamine collected by microdialysis reflects a pool of releasable neurotransmitter.
Subject(s)
Dopamine/physiology , Motor Cortex/physiology , Parietal Lobe/physiology , Animals , Cerebral Decortication , Chromatography, High Pressure Liquid , Dialysis/methods , Dopamine/metabolism , Kainic Acid/physiology , Male , Motor Cortex/metabolism , Parietal Lobe/metabolism , Potassium Chloride/metabolism , Rats , Rats, Inbred Strains , Stereotaxic TechniquesABSTRACT
6-Cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX; FG 9065) is a new excitatory amino acid antagonist. In the spinal cord it has been reported to selectively block responses to acidic amino acids acting at receptors of the non-N-methyl-D-aspartate (non-NMDA) type. Here we report that in rat hippocampal slices bathed in Mg2+-free medium 10 microM CNQX reversibly blocks responses to alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), quisqualate and kainate but not NMDA. The synaptic response evoked by low frequency stimulation of Schaffer collateral-commissural fibres in 1 mM Mg2+-containing medium is completely blocked by this concentration of CNQX. In contrast the synaptic response evoked in Mg2+-free medium is not fully blocked by CNQX. The CNQX-insensitive component is, however, abolished by addition of a selective NMDA antagonist. The use of CNQX has allowed for the first time selective synaptic activation of NMDA receptors in the hippocampus.
Subject(s)
Hippocampus/drug effects , Quinoxalines/physiology , Receptors, Neurotransmitter/physiology , Synapses/drug effects , Animals , Female , Hippocampus/physiology , Ibotenic Acid/analogs & derivatives , Ibotenic Acid/physiology , Kainic Acid/physiology , Oxadiazoles/physiology , Quisqualic Acid , Rats , Receptors, N-Methyl-D-Aspartate , Synapses/physiology , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic AcidABSTRACT
The binding kinetics, pharmacological properties and regional ontogeny of L-[3H]glutamic acid Na+-independent and [3H]kainic acid binding sites were studied in preparations of chick brain. One binding component was found for L-[3H]glutamic acid with a Kd value of 176 x 10(9) M. For [3H]kainic acid two binding components were found in the hemispheres, optic lobes and brain stem, one with high affinity and a Kd value of 12.5 x 10(9) M and one with low affinity and a Kd value of 260 x 10(9) M. In cerebellum only one binding site was detected for [3H]kainic acid with a Kd value of 144 x 10(9) M. The ontogeny of L-[3H]glutamic acid and [3H]kainic acid binding sites was studied using membrane preparations (48,000 g pellet) of hemispheres, optic lobes, brain stem and cerebellum. Binding of L-[3H]glutamic acid was already significant in all brain regions by embryonic day 11 but major increases in total receptor number per brain region or per mg of protein were apparent by embryonic day 19 and especially after hatching. Cerebral hemispheres, optic lobes and brain stem showed few [3H]kainic acid binding sites by day 13 in ovo. An increase follows which, in hemispheres and optic lobes, continues at the same rate during the first two weeks after hatching. In cerebellum, by contrast, the kainic acid binding site is almost undetectable until embryonic day 15. The appearance of these binding sites in cerebellum takes place during the restricted period between days 15 in ovo and 5 post-hatching. This pattern of development of [3H]kainic acid binding sites almost parallels the developmental patterns of the molecular layer of chick cerebellum and it is consistent with the results of our autoradiographic study showing that the great majority of kainic acid binding sites are localized in the molecular layer.
