NMDA receptors with incomplete Mg²⁺ block enable low-frequency transmission through the cerebellar cortex

J Neurosci. 2012 May 16;32(20):6878-93. doi: 10.1523/JNEUROSCI.5736-11.2012.


The cerebellar cortex coordinates movements and maintains balance by modifying motor commands as a function of sensory-motor context, which is encoded by mossy fiber (MF) activity. MFs exhibit a wide range of activity, from brief precisely timed high-frequency bursts, which encode discrete variables such as whisker stimulation, to low-frequency sustained rate-coded modulation, which encodes continuous variables such as head velocity. While high-frequency MF inputs have been shown to activate granule cells (GCs) effectively, much less is known about sustained low-frequency signaling through the GC layer, which is impeded by a hyperpolarized resting potential and strong GABA(A)-mediated tonic inhibition of GCs. Here we have exploited the intrinsic MF network of unipolar brush cells to activate GCs with sustained low-frequency asynchronous MF inputs in rat cerebellar slices. We find that low-frequency MF input modulates the intrinsic firing of Purkinje cells, and that this signal transmission through the GC layer requires synaptic activation of Mg²⁺-block-resistant NMDA receptors (NMDARs) that are likely to contain the GluN2C subunit. Slow NMDAR conductances sum temporally to contribute approximately half the MF-GC synaptic charge at hyperpolarized potentials. Simulations of synaptic integration in GCs show that the NMDAR and slow spillover-activated AMPA receptor (AMPAR) components depolarize GCs to a similar extent. Moreover, their combined depolarizing effect enables the fast quantal AMPAR component to trigger action potentials at low MF input frequencies. Our results suggest that the weak Mg²⁺ block of GluN2C-containing NMDARs enables transmission of low-frequency MF signals through the input layer of the cerebellar cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Cerebellar Cortex / drug effects
  • Cerebellar Cortex / metabolism
  • Cerebellar Cortex / physiology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • In Vitro Techniques
  • Magnesium / pharmacology*
  • Male
  • Nerve Fibers / physiology
  • Neurons / physiology
  • Purkinje Cells / physiology
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Resorcinols / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Receptors, N-Methyl-D-Aspartate
  • Resorcinols
  • 3,5-dihydroxyphenylglycine
  • Magnesium
  • Glycine