MODULATION OF PRESYNAPTIC AND POSTSYNAPTIC CALCIUM DYNAMICS BY IONOTROPIC GLUTAMATE RECEPTORS AT A PLASTIC SYNAPSE

This study was conducted to assess the role of ionotropic glutamate re ceptors in the modulation of calcium dynamics on both sides of a verte brate plastic synapse. Retrograde labeling of neuronal elements with h igh-affinity calcium-sensitive dyes was used in conjunction with confo cal imaging techniques in an in vitro lamprey brain stem preparation. A prolonged calcium transient was measured both pre-and postsynaptical ly in response to a period of high-frequency (''tetanic'') stimulation to the vestibulospinal-reticulospinal synapse. The ionotropic glutama te receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (10 mu M) and D,L-2-amino-5-phosphonopentanoate (D,L-AP5; 100 mu M) reduced the calcium signal in both compartments of the synapse. The presynaptic D ,L-APS-sensitive component was enhanced markedly by the removal of Mg2 + from the superfusate. Increasing the extracellular stimulus intensit y progressively augmented the presynaptic calcium signal, suggesting t he recruitment of excitatory axo-axonic inputs onto these fibers. Furt her, the presence of an excitatory amino acid-mediated presynaptic pot ential underlying a component of the Ca2+ signal was demonstrated by e lectrophysiological recordings from vestibulospinal axons. Bath applic ation of agonist, in the presence of tetrodotoxin (1 mu M), confirmed the existence of N-methyl-D-aspartate receptors at the presynaptic ele ment capable of modulating calcium levels. The postsynaptic Ca2+ respo nse, which is known to be necessary for long-term potentiation (LTP) i nduction 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 syn apse specificity of LTP induction previously demonstrated. In summary, we have demonstrated the existence of physiologically activated presy naptic ionotropic glutamate receptors that are capable of modulating l evels of intracellular calcium and have highlighted the importance of receptor-mediated increases in postsynaptic calcium for neuronal plast icity in the lamprey.