Properties and plasticity of paired-pulse depression at a central synapse

Synaptic depression was studied at the axo-axonic connection between the go ldfish Mauthner axon and identified cranial relay interneurons using simult aneous presynaptic and postsynaptic recordings and a paired-pulse stimulus paradigm. We used interstimulus intervals (ISIs) ranging from 10 msec to 1 sec and a cycle time of similar to 5 sec. Depression (Delta EPSP/EPSP1) was maximal at the shorter intervals (80%) and decreased exponentially with a tau similar to 400 msec (360 +/- 107 msec, mean +/- SD). We found the ampli tudes of the first and second EPSP were not correlated, indicating the magn itude of depression does not depend on the amount of transmitter released b y the conditioning stimulus. At short ISIs, the latency of EPSP2 was 23% lo nger than that of EPSP1 and recovered to control with tau similar to 400 ms ec, whereas rise time and decay time were not altered significantly. The la tency distribution, which is determined by the timing of the first quantum released each trial, was used to derive a( t), the rate of evoked exocytosi s after an action potential. a( t) was biphasic, and both components were c onsistently delayed during depression. Presynaptic manipulations of putativ e intracellular regulatory pathways, such as Ca2+ and GTP gamma S injection s, preferentially affected the amplitude of EPSP1 or EPSP2. These results a re not consistent with simple depletion of the available pool of synaptic v esicles as the major mechanism underlying depression. They rather suggest t hat it is attributable to a modification or refractoriness of the release p rocess and that there may be multiple pathways subserving evoked exocytosis .