INDUCTION OF CEREBELLAR LONG-TERM DEPRESSION IN CULTURE REQUIRES POSTSYNAPTIC ACTION OF SODIUM-IONS

Cerebellar long-term depression (LTD) is a persistent attenuation of t he parallel fiber-Purkinje neuron (PF-PN) synapse induced by conjuncti ve stimulation of PF and climbing fiber (CF) inputs. A similar phenome non is seen in the voltage-clamped PN in tissue culture when iontophor etic quisqualate application and PN depolarization are substituted for PF and CF stimulation, respectively. In this model, LTD induction req uires activation of both AMPA and metabotropic receptors, together wit h PN depolarization. We have sought to determine the role of the AMPA receptor in LTD induction. The AMPA receptor does not appear to exert its effect by directly gating Cal+ influx. Replacement of external Na during quisqualate/depolarization conjunction with permeant ions caus ed a blockade of LTD induction, suggesting that Na+ influx through the AMPA-associated channel is necessary for this process. Similarly, pai ring quisqualate pulses with depolarizing steps near E(Na) also failed to induce LTD. The present results indicate that postsynaptic Na+ inf lux is necessary for LTD induction. While a portion of the relevant Na + influx is provided by voltage-gated channels, the AMPA-associated io n channel is most important in this regard.