Evidence for NMDA and mGlu Receptor-Dependent Long-Term Potentiation of Mossy Fiber-Granule Cell Transmission in Rat Cerebellum

J Neurophysiol. 1999 Jan;81(1):277-87. doi: 10.1152/jn.1999.81.1.277.

Abstract

Long-term potentiation (LTP) is a form of synaptic plasticity that can be revealed at numerous hippocampal and neocortical synapses following high-frequency activation of N-methyl--aspartate (NMDA) receptors. However, it was not known whether LTP could be induced at the mossy fiber-granule cell relay of cerebellum. This is a particularly interesting issue because theories of the cerebellum do not consider or even explicitly negate the existence of mossy fiber-granule cell synaptic plasticity. Here we show that high-frequency mossy fiber stimulation paired with granule cell membrane depolarization (-40 mV) leads to LTP of granule cell excitatory postsynaptic currents (EPSCs). Pairing with a relatively hyperpolarized potential (-60 mV) or in the presence of NMDA receptor blockers [5-amino--phosphonovaleric acid (APV) and 7-chloro-kynurenic acid (7-Cl-Kyn)] prevented LTP, suggesting that the induction process involves a voltage-dependent NMDA receptor activation. Metabotropic glutamate receptors were also involved because blocking them with (+)-alpha-methyl-4-carboxyphenyl-glycine (MCPG) prevented potentiation. At the cytoplasmic level, EPSC potentiation required a Ca2+ increase and protein kinase C (PKC) activation. Potentiation was expressed through an increase in both the NMDA and non-NMDA receptor-mediated current and by an NMDA current slowdown, suggesting that complex mechanisms control synaptic efficacy during LTP. LTP at the mossy fiber-granule cell synapse provides the cerebellar network with a large reservoir for memory storage, which may be needed to optimize pattern recognition and, ultimately, cerebellar learning and computation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebellum / cytology
  • Cerebellum / drug effects
  • Cerebellum / physiology*
  • Electric Stimulation
  • Electrophysiology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • In Vitro Techniques
  • Long-Term Potentiation / physiology*
  • Membrane Potentials / physiology
  • Nerve Fibers / physiology*
  • Patch-Clamp Techniques
  • Protein Kinase C / biosynthesis
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / physiology*
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Protein Kinase C