Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Norepinephrine controls the gain of the inhibitory circuit in the cerebellar input layer

Frederic Lanore, Jason S. Rothman, Diccon Coyle, R. Angus Silver
doi: https://doi.org/10.1101/567172
Frederic Lanore
Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jason S. Rothman
Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Diccon Coyle
Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R. Angus Silver
Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Summary

Golgi cells (GoCs) are the main inhibitory interneurons in the input layer of the cerebellar cortex and are electrically coupled together, forming syncytia. GoCs control the excitability of granule cells (GCs) through feedforward, feedback and spillover-mediated inhibition. The GoC circuit therefore plays a central role in determining how sensory and motor information is transformed as it flows through the cerebellar input layer. Recent work has shown that GCs are activated when animals perform active behaviours, but the underlying mechanisms remain poorly understood. Norepinephrine (NE), also known as noradrenaline, is a powerful modulator of network function during active behavioral states and the axons of NE-releasing neurons in the locus coeruleus innervate the cerebellar cortex. Here we show that NE hyperpolarizes the GoC membrane potential, decreases spontaneous firing and reduces the gain of the spike frequency versus input-current relationship. The GoC membrane hyperpolarization can be mimicked with an α2-noradrenergic agonist, inhibited with a specific α2 antagonist and is abolished when G protein-coupled inwardly-rectifying potassium (GIRK) channels are blocked. Moreover, NE reduces the effective electrical coupling between GoCs through a persistent sodium current (INaP)-dependent mechanism. Our results suggest that NE controls the gain of the GoC inhibitory circuit by modulating membrane conductances that act to reduce membrane excitability and decrease electrical coupling. These mechanisms appear configured to reduce the level of GoC inhibition onto GCs during active behavioural states.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted March 04, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Norepinephrine controls the gain of the inhibitory circuit in the cerebellar input layer
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Norepinephrine controls the gain of the inhibitory circuit in the cerebellar input layer
Frederic Lanore, Jason S. Rothman, Diccon Coyle, R. Angus Silver
bioRxiv 567172; doi: https://doi.org/10.1101/567172
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Norepinephrine controls the gain of the inhibitory circuit in the cerebellar input layer
Frederic Lanore, Jason S. Rothman, Diccon Coyle, R. Angus Silver
bioRxiv 567172; doi: https://doi.org/10.1101/567172

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (3701)
  • Biochemistry (7827)
  • Bioengineering (5699)
  • Bioinformatics (21349)
  • Biophysics (10607)
  • Cancer Biology (8212)
  • Cell Biology (11978)
  • Clinical Trials (138)
  • Developmental Biology (6790)
  • Ecology (10427)
  • Epidemiology (2065)
  • Evolutionary Biology (13912)
  • Genetics (9733)
  • Genomics (13112)
  • Immunology (8176)
  • Microbiology (20076)
  • Molecular Biology (7882)
  • Neuroscience (43186)
  • Paleontology (321)
  • Pathology (1285)
  • Pharmacology and Toxicology (2269)
  • Physiology (3365)
  • Plant Biology (7259)
  • Scientific Communication and Education (1317)
  • Synthetic Biology (2012)
  • Systems Biology (5551)
  • Zoology (1135)