Quantification of spread of cerebellar long-term depression with chemical two-photon uncaging of glutamate

Localized. chemical two-photon photolysis of caged glutamate was used to ma p the changes in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-t ype glutamate receptors caused by long-term synaptic depression (LTD) in ce rebellar Purkinje cells. LTD produced by pairing parallel fiber activity wi th depolarization was accompanied by a decline in the response of Purkinje cells to uncaged glutamate that accounted for both the time course and magn itude of LTD. This depression of glutamate responses was observed not only at the site of parallel fiber stimulation but also at more distant sites. T he amount of LTD decreased with distance and was half-maximal 50 mu m away from the site of parallel fiber activity. Estimation of the number of paral lel fibers active during LTD induction indicates that LTD modified glutamat e receptors not only at active synapses but also at 600 times as many inact ive synapses on a single Purkinje cell. Therefore. both active and inactive parallel fiber synapses can undergo changes at a postsynaptic locus as a r esult of associative pre- and postsynaptic activity.