Potentiation of mossy fiber EPSCs in the cerebellar nuclei by NMDA receptor activation followed by postinhibitory rebound current

Neuron. 2006 Jul 6;51(1):113-23. doi: 10.1016/j.neuron.2006.05.021.


Behavioral and computational studies predict that synaptic plasticity of excitatory mossy fiber inputs to cerebellar nuclear neurons is required for associative learning, but standard tetanization protocols fail to potentiate nuclear cell EPSCs in mouse cerebellar slices. Nuclear neurons fire action potentials spontaneously unless strongly inhibited by Purkinje neurons, raising the possibility that plasticity-triggering signals in these cells differ from those at classical Hebbian synapses. Based on predictions of neuronal activity during delay eyelid conditioning, we developed quasi-physiological induction protocols consisting of high-frequency mossy fiber stimulation and postsynaptic hyperpolarization. Robust, NMDA receptor-dependent potentiation of nuclear cell EPSCs occurred with protocols including a 150-250 ms hyperpolarization in which mossy fiber stimulation preceded a postinhibitory rebound depolarization. Mossy fiber stimulation potentiated EPSCs even when postsynaptic spiking was prevented by voltage-clamp, as long as rebound current was evoked. These data suggest that Purkinje cell inhibition guides the strengthening of excitatory synapses in the cerebellar nuclei.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Association Learning / physiology
  • Cerebellar Nuclei / drug effects
  • Cerebellar Nuclei / physiology*
  • Chelating Agents / pharmacology
  • Conditioning, Eyelid / physiology
  • Electric Stimulation / methods
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Fibers / drug effects
  • Nerve Fibers / physiology*
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neuronal Plasticity / physiology*
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology
  • Purkinje Cells / physiology
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology


  • Chelating Agents
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate