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Article Dans Une Revue Journal of Neuroscience Année : 2012

NMDA Receptors with Incomplete Mg2+ Block Enable Low-Frequency Transmission through the Cerebellar Cortex

Eric J. Schwartz
  • Fonction : Auteur
Jason S. Rothman
  • Fonction : Auteur
Guillaume P. Dugue
Charly Rousseau
  • Fonction : Auteur
R. Angus Silver
  • Fonction : Auteur
Stephane Dieudonne
  • Fonction : Auteur

Résumé

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 GClayer, which is impeded by a hyperpolarized resting potential and strong GABAA-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 weakMg(2+) block of GluN2C-containing NMDA Rs enables transmission of low-frequency MF signals through the input layer of the cerebellar cortex.

Dates et versions

hal-01542380 , version 1 (19-06-2017)

Identifiants

Citer

Eric J. Schwartz, Jason S. Rothman, Guillaume P. Dugue, Marco Diana, Charly Rousseau, et al.. NMDA Receptors with Incomplete Mg2+ Block Enable Low-Frequency Transmission through the Cerebellar Cortex. Journal of Neuroscience, 2012, 32 (20), pp.6878-6893. ⟨10.1523/JNEUROSCI.5736-11.2012⟩. ⟨hal-01542380⟩
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