Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

Acetylcholine Modulates Cerebellar Granule Cell Spiking by Regulating the Balance of Synaptic Excitation and Inhibition.

Publication ,  Journal Article
Fore, TR; Taylor, BN; Brunel, N; Hull, C
Published in: J Neurosci
April 1, 2020

Sensorimotor integration in the cerebellum is essential for refining motor output, and the first stage of this processing occurs in the granule cell layer. Recent evidence suggests that granule cell layer synaptic integration can be contextually modified, although the circuit mechanisms that could mediate such modulation remain largely unknown. Here we investigate the role of ACh in regulating granule cell layer synaptic integration in male rats and mice of both sexes. We find that Golgi cells, interneurons that provide the sole source of inhibition to the granule cell layer, express both nicotinic and muscarinic cholinergic receptors. While acute ACh application can modestly depolarize some Golgi cells, the net effect of longer, optogenetically induced ACh release is to strongly hyperpolarize Golgi cells. Golgi cell hyperpolarization by ACh leads to a significant reduction in both tonic and evoked granule cell synaptic inhibition. ACh also reduces glutamate release from mossy fibers by acting on presynaptic muscarinic receptors. Surprisingly, despite these consistent effects on Golgi cells and mossy fibers, ACh can either increase or decrease the spike probability of granule cells as measured by noninvasive cell-attached recordings. By constructing an integrate-and-fire model of granule cell layer population activity, we find that the direction of spike rate modulation can be accounted for predominately by the initial balance of excitation and inhibition onto individual granule cells. Together, these experiments demonstrate that ACh can modulate population-level granule cell responses by altering the ratios of excitation and inhibition at the first stage of cerebellar processing.SIGNIFICANCE STATEMENT The cerebellum plays a key role in motor control and motor learning. While it is known that behavioral context can modify motor learning, the circuit basis of such modulation has remained unclear. Here we find that a key neuromodulator, ACh, can alter the balance of excitation and inhibition at the first stage of cerebellar processing. These results suggest that ACh could play a key role in altering cerebellar learning by modifying how sensorimotor input is represented at the input layer of the cerebellum.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

April 1, 2020

Volume

40

Issue

14

Start / End Page

2882 / 2894

Location

United States

Related Subject Headings

  • Synaptic Transmission
  • Rats, Sprague-Dawley
  • Rats
  • Neurons
  • Neurology & Neurosurgery
  • Neural Inhibition
  • Models, Neurological
  • Mice
  • Male
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Fore, T. R., Taylor, B. N., Brunel, N., & Hull, C. (2020). Acetylcholine Modulates Cerebellar Granule Cell Spiking by Regulating the Balance of Synaptic Excitation and Inhibition. J Neurosci, 40(14), 2882–2894. https://doi.org/10.1523/JNEUROSCI.2148-19.2020
Fore, Taylor R., Benjamin N. Taylor, Nicolas Brunel, and Court Hull. “Acetylcholine Modulates Cerebellar Granule Cell Spiking by Regulating the Balance of Synaptic Excitation and Inhibition.J Neurosci 40, no. 14 (April 1, 2020): 2882–94. https://doi.org/10.1523/JNEUROSCI.2148-19.2020.
Fore, Taylor R., et al. “Acetylcholine Modulates Cerebellar Granule Cell Spiking by Regulating the Balance of Synaptic Excitation and Inhibition.J Neurosci, vol. 40, no. 14, Apr. 2020, pp. 2882–94. Pubmed, doi:10.1523/JNEUROSCI.2148-19.2020.
Fore TR, Taylor BN, Brunel N, Hull C. Acetylcholine Modulates Cerebellar Granule Cell Spiking by Regulating the Balance of Synaptic Excitation and Inhibition. J Neurosci. 2020 Apr 1;40(14):2882–2894.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

April 1, 2020

Volume

40

Issue

14

Start / End Page

2882 / 2894

Location

United States

Related Subject Headings

  • Synaptic Transmission
  • Rats, Sprague-Dawley
  • Rats
  • Neurons
  • Neurology & Neurosurgery
  • Neural Inhibition
  • Models, Neurological
  • Mice
  • Male
  • Female