Abstract
Although activity-dependent changes in synaptic strength as a cellular substrate for leaning and memory have been extensively studied, activity-dependent maintenance of basal synaptic strength is not well understood. We examined the effect of chronic in vivo inhibition of synaptic inputs on the strength of parallel fiber (PF)-Purkinje cell (PC) synapses in the adult mouse cerebellar cortex. To suppress the PF activity, the NMDA-type glutamate receptors on cerebellar granule cells was blocked by continuous infusion of APV from an ethylene-vinyl acetate copolymer implant placed over the cerebellar cortex on postnatal day 23. Three to seven days later, PF-evoked excitatory post-synaptic currents (EPSCs) were recorded from PCs in acute slices. The chronic APV application resulted in increase in the paired-pulse ratio and the coefficient of variation of EPSC amplitude, suggesting a decrease in the probability of neurotransmitter release from PFs. On the other hand, the postsynaptic sensitivity to transmitters seemed unchanged. Furthermore, persistent suppression of one of the postsynaptic signaling pathways, namely the type-1 metabotropic glutamate receptor (mGluR1)-IP3 signaling pathway, also decreased the probability of transmitter release from PFs. These results suggest that the strength of PF-PC synapses is presynaptically maintained by the PF activity, and that the mGluR-IP3 signaling pathway in PCs is involved in a retrograde regulation of the presynaptic function. [Jpn J Physiol 55 Suppl:S146 (2005)]
