Modulation of transmission during trains at a cerebellar synapse

J Neurosci. 2000 Feb 15;20(4):1348-57. doi: 10.1523/JNEUROSCI.20-04-01348.2000.


Activity-dependent processes dynamically regulate synapses on the time scale of milliseconds to seconds. Here, we examine the factors governing synaptic strength during repetitive stimulation, both in control conditions and during presynaptic inhibition. Field recordings of presynaptic volleys, optical measurements of presynaptic calcium, and voltage-clamp recordings of postsynaptic currents were used to examine parallel fiber to Purkinje cell synapses in cerebellar brain slices at 34 degrees C. In control conditions, regular stimulus trains (1-50 Hz) evoked up to a 250% peak synaptic enhancement, whereas during irregular stimulation, a threefold variability in EPSC amplitude was observed. When initial EPSC amplitudes were reduced by 50%, either by lowering external calcium or by activating adenosine A(1) or GABA(B) receptors, the peak enhancement during regular trains was 500%, and synaptic variability during irregular trains was nearly sixfold. By contrast, changes in fiber excitability and calcium influx per pulse were small during trains. Presynaptic calcium measurements indicated that by pulse 10, stimulus-evoked calcium influx had increased by approximately 15%, which on the basis of the measured relationship between calcium influx and release corresponds to an EPSC enhancement of 50%. This enhancement was the same in all experimental conditions, even in the presence of N(6)-cyclopentyladenosine or baclofen, suggesting that repetitive stimulation does not relieve the G-protein inhibition of calcium channels by these modulators. Therefore, for our experimental conditions, changes in synaptic strength during trains are primarily attributable to residual calcium (Ca(res))-dependent short-term plasticities, and the actions of neuromodulators during repetitive stimulation result from their inhibition of initial calcium influx and the resulting effects on Ca(res) and calcium-driven processes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Baclofen / pharmacology
  • Calcium / metabolism
  • Calcium / pharmacology
  • Cerebellum / physiology*
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • GABA Antagonists / pharmacology
  • GTP-Binding Proteins / physiology
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • In Vitro Techniques
  • Nerve Fibers / drug effects
  • Nerve Fibers / physiology
  • Phosphinic Acids / pharmacology
  • Presynaptic Terminals / physiology
  • Propanolamines / pharmacology
  • Purinergic P1 Receptor Antagonists
  • Purkinje Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-B / physiology
  • Receptors, Purinergic P1 / physiology
  • Synapses / drug effects
  • Synapses / physiology*
  • Xanthines / pharmacology


  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Phosphinic Acids
  • Propanolamines
  • Purinergic P1 Receptor Antagonists
  • Receptors, GABA-B
  • Receptors, Purinergic P1
  • Xanthines
  • cyclopropyl-4-phosphonophenylglycine
  • CGP 55845A
  • 1,3-dipropyl-8-cyclopentylxanthine
  • GTP-Binding Proteins
  • Baclofen
  • Calcium
  • Glycine