Paired-pulse facilitation of multivesicular release and intersynaptic spillover of glutamate at rat cerebellar granule cell-interneurone synapses

J Physiol. 2012 Nov 15;590(22):5653-75. doi: 10.1113/jphysiol.2012.234070. Epub 2012 Aug 28.


A simple form of presynaptic plasticity, paired-pulse facilitation (PPF), has been explained as a transient increase in the probability of vesicular release. Using the whole-cell patch-clamp technique to record synaptic activity in rat cerebellar slices, we found different forms of presynaptically originated short-term plasticity during glutamatergic excitatory neurotransmission from granule cells (GCs) to molecular-layer interneurones (INs). Paired-pulse activation of GC axons at short intervals (30-100 ms) elicited not only a facilitation in the peak amplitude (PPF(amp)), but also a prolongation in the decay-time constant (PPP(decay)) of the EPSCs recorded from INs. The results of pharmacological tests and kinetics analyses suggest that the mechanisms underlying the respective types of short-term plasticity were different. PPF(amp) was elicited by a transient increase in the number of released vesicles. On the other hand, PPP(decay) was caused not only by delayed release as has been reported but also by extrasynaptic spillover of the GC transmitter and the subsequent intersynaptic pooling. Both PPF(amp) and PPP(decay) closely rely on repetitive-activation-induced multivesicular release. Using a dynamic clamp technique, we further examined the physiological significance of different presynaptic plasticity, and found that PPF(amp) and PPP(decay) can differentially encode and process neuronal information by influencing the total synaptic charge transferred to postsynaptic INs to reflect activation frequency of the presynaptic GCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebellar Cortex / cytology
  • Cerebellar Cortex / physiology
  • Excitatory Postsynaptic Potentials
  • Exocytosis
  • GABA Antagonists / pharmacology
  • Glutamic Acid / metabolism*
  • Interneurons / cytology
  • Interneurons / physiology*
  • Neuronal Plasticity
  • Rats
  • Rats, Wistar
  • Synapses / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Synaptic Vesicles / physiology*


  • GABA Antagonists
  • Glutamic Acid