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- Title
NMDA Receptors with Incomplete Mg<sup>2</sup><sup>+</sup> Block Enable Low-Frequency Transmission through the Cerebellar Cortex.
- Authors
Schwartz, Eric J.; Rothman, Jason S.; Dugué, Guillaume P.; Diana, Marco; Silver, R. Angus; Dieudonné, Stéphane
- Abstract
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, muchless isknownabout sustained low-frequency signaling through the GC layer, 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+-blockresistant 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 NMDAR senables transmission of low-frequency MF signals through the input layer of the cerebellar cortex.
- Subjects
METHYL aspartate receptors; NEURAL transmission; CEREBELLAR cortex; MAGNESIUM isotopes; GABA; NEURAL circuitry; AMPA receptors
- Publication
Journal of Neuroscience, 2012, Vol 32, Issue 20, p6878
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5736-11.2012