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

By E. Schwartz, J. Rothman, G. Dugué, Marco A. Diana, Charly V. Rousseau, R. Silver, S. Dieudonné. 2012

48 citations recorded by the source corpus.

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 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 weak Mg2+ block of GluN2C-containing NMDARs enables transmission of low-frequency MF signals through the input layer of the cerebellar cortex.

Subfields: Cellular and Molecular Neuroscience, Neurology, Sensory Systems

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. R. Silver
2. A. Lorincz
3. Z. Nusser
4. Egidio D'Angelo
5. Guy O. Billings
6. Nicholas P. Franks

In Neurology

1. R. Silver
2. A. Lorincz
3. N. A. Cayco-Gajic

In Sensory Systems

1. R. Silver
2. Egidio D'Angelo
3. Z. Nusser

Citations in the corpus

• Re-evaluating circuit mechanisms underlying pattern separation (2019, neutral): “10 milliseconds, an order of magnitude larger than the timescale for synaptic integration of granule cells (D’Angelo et al., 1995; Schwartz et al., 2012; Rothman et al., 2009; Billings et al 2014).”
• Granule Cell Ascending Axon Excitatory Synapses onto Golgi Cells Implement a Potent Feedback Circuit in the Cerebellar Granular Layer (2013, background): “…to GoC excitation during repetitive mf activity It is well known that the excitation of GrCs by mf inputs may require the temporal summation of multiple synaptic inputs during low-frequency asynchronous activity (Schwartz et al., 2012) or during high-frequency trains (D’Angelo et al., 1995).”
• Network Structure within the Cerebellar Input Layer Enables Lossless Sparse Encoding (2014, methodology): “…build up over time during rate-coded MF input (Arenz et al., 2008; DiGregorio et al., 2002; Schwartz et al., 2012), (3) GCs have only two to seven excitatory MF inputs, and (4) multiple MF inputs are typically required to reach spike threshold (Jörntell and Ekerot, 2006; Schwartz et al., 2012).”