Modulation of pre- and postsynaptic calcium dynamics by ionotropic glutamate receptors at a plastic synapse.
This study was conducted to assess the role of ionotropic glutamate receptors in the modulation of calcium dynamics on both sides of a vertebrate plastic synapse. Retrograde labeling of neuronal elements with high-affinity calcium-sensitive dyes was used in conjunction with confocal imaging techniques in an in vitro lamprey brain stem preparation. A prolonged calcium transient was measured both pre- and postsynaptically in response to a period of high-frequency ("tetanic") stimulation to the vestibulospinal-reticulospinal synapse. The ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) and D,L-2-amino-5-phosphonopentanoate (D,L-AP5; 100 microM) reduced the calcium signal in both compartments of the synapse. The presynaptic D,L-AP5-sensitive component was enhanced markedly by the removal of Mg2+ from the superfusate. Increasing the extracellular stimulus intensity progressively augmented the presynaptic calcium signal, suggesting the recruitment of excitatory axo-axonic inputs onto these fibers. Further, the presence of an excitatory amino acid-mediated presynaptic potential underlying a component of the Ca2+ signal was demonstrated by electrophysiological recordings from vestibulospinal axons. Bath application of agonist, in the presence of tetrodotoxin (1 microM), confirmed the existence of N-methyl-D-aspartate receptors at the presynaptic element capable of modulating calcium levels. The postsynaptic Ca2+ response, which is known to be necessary for long-term potentiation (LTP) induction at this synapse, was localized to areas of the dendritic tree that correlated with the location of known synaptic inputs; thus the synaptically activated rise in postsynaptic calcium may confer the synapse specificity of LTP induction previously demonstrated. In summary, we have demonstrated the existence of physiologically activated presynaptic ionotropic glutamate receptors that are capable of modulating levels of intracellular calcium and have highlighted the importance of receptor-mediated increases in postsynaptic calcium for neuronal plasticity in the lamprey.
Schwartz
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Department of Physiology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Alford
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D003712:Dendrites / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005470:Fluorometry; D066298:In Vitro Techniques; D007798:Lampreys; D018613:Microscopy, Confocal; D009473:Neuronal Plasticity / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013746:Tetany
D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium