Interaction between facilitation and depression at a large CNS synapse reveals mechanisms of short term plasticity

MARTIN MÜLLER; JUAN D. GOUTMAN; OLEXEIY KOCHUBEY; RALF SCHNEGGENBURGER

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Año: 2010 vol. 30 p. 2007 - 2016

0270-6474

The two fundamental forms of short-term plasticity, short-term depression and facilitation, coexist at most synapses, but little is known about their interaction. Here, we studied the interplay between short-term depression and facilitation at calyx of Held synapses. Stimulation at a "low" frequency of 10 - 20 Hz, a frequency which is in the range of the spontaneous activity of these auditory neurons in vivo, induced synaptic depression. Surprisingly, an instantaneous increase of the stimulation frequency to 100 - 200 Hz following the low-frequency train uncovered a robust facilitation of EPSCs relative to the pre-depressed amplitude level. This facilitation decayed rapidly (~ 30 ms) and depended on presynaptic residual Ca2+, but it was not caused by Ca2+ current facilitation. To probe the release probability of the remaining readily-releasable vesicles, we made presynaptic Ca2+ uncaging experiments in the pre-depressed state of the synapse. We found that low-frequency stimulation depletes the fast-releasable vesicle pool (FRP) down to ~ 40% of control, and that the remaining  of FRP vesicles are released with ~ 2-fold slower release kinetics, indicating a hitherto unknown intrinsic heterogeneity amongst FRP vesicles. Thus, vesicles with an intrinsically lower release probability predominate after low frequency stimulation, and undergo facilitation during the onset of subsequent high-frequency trains. Facilitation in the pre-depressed state of the synapse might help to stabilize the amount of transmitter release at the onset of high-frequency firing at these auditory synapses.