NMDA receptor-mediated control of presynaptic calcium and neurotransmitterrelease

Before action potential-evoked Ca2+ transients, basal presynaptic Ca2+ conc entration may profoundly affect the amplitude of subsequent neurotransmitte r release. Reticulospinal axons of the lamprey spinal cord receive glutamat ergic synaptic input. We have investigated the effect of this input on pres ynaptic Ca2+ concentrations and evoked release of neurotransmitter. Paired recordings were made between reticulospinal axons and the neurons that make axo-axonic synapses onto those axons. Both excitatory and inhibitory paire d-cell responses were recorded in the axons, Excitatory synaptic inputs wer e blocked by the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-di one (CNQX; 10 mu M) and by the NMDA receptor antagonist 2-amino-5-phosphono pentanoate (AP-5; 50 mu M). Application of NMDA evoked an increase in presy naptic Ca2+ in reticulospinal axons. Extracellular stimulation evoked Ca2transients in axons when applied either directly over the axon or lateral t o the axons. Transients evoked by the two types of stimulation differed in magnitude and sensitivity to AP-5. Simultaneous microelectrode recordings f rom the axons during Ca2+ imaging revealed that stimulation of synaptic inp uts directed to the axons evoked Ca2+ entry. By the use of paired-cell reco rdings between reticulospinal axons and their postsynaptic targets, NMDA re ceptor activation was shown to enhance evoked release of transmitter from t he axons that received axoaxonic inputs. When the synaptic input to the axo n was stimulated before eliciting an action potential in the axon, transmit ter release from the axon was enhanced. We conclude that NMDA receptor-medi ated input to reticulospinal axons increases basal Ca2+ within the axons an d that this Ca2+ is sufficient to enhance release from the axons.