Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Localised adenosine signalling provides fine-tuned negative feedback over a wide dynamic range of neocortical network activities

Tools
- Tools
+ Tools

Wall, Mark J. and Richardson, Magnus J. E. (2015) Localised adenosine signalling provides fine-tuned negative feedback over a wide dynamic range of neocortical network activities. Journal of Neurophysiology, 113 (3). pp. 871-882. doi:10.1152/jn.00620.2014

[img] PDF
WRAP_9976826-lf-080115-wall_and_richardson.pdf - Accepted Version
Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer.

Download (1373Kb)
Official URL: http://dx.doi.org/10.1152/jn.00620.2014

Request Changes to record.

Abstract

Although the patterns of activity produced by neocortical networks are becoming better understood, how these states are activated, sustained and terminated still remains unclear. Negative feedback by the endogenous neuromodulator adenosine could potentially play an important role, as it can be released by activity and there is dense A1 receptor expression in the neocortex. Using electrophysiology, biosensors and modelling, we have investigated the properties of adenosine signalling during physiological and pathological network activity in rat neocortical slices. Both low and high-rate network activities were reduced by A1 receptor activation and enhanced by block of A1 receptors, consistent with activity-dependent adenosine release. Since the A1 receptors were neither saturated nor completely unoccupied during either low or high-rate activity, adenosine signalling provides a negative feedback mechanism with a wide dynamic range. Modelling and biosensor experiments show that during high-rate activity, increases in extracellular adenosine concentration are highly localised and are uncorrelated over short distances that are certainly less than 500 μm. Modelling also predicts that the slow time course of the purine waveform cannot be from diffusion from distal release sites but more likely results from uptake and metabolism. The inability to directly measure adenosine release during low-rate activity, although it is present, is probably a consequence of small localised increases in adenosine concentration which are rapidly diminished by diffusion and active removal mechanisms. Saturation of such removal mechanisms when higher concentrations of adenosine are released, results in the accumulation of inosine, explaining the strong purine signal during high-rate activity.

Item Type: Journal Article
Divisions: Faculty of Science > Life Sciences (2010- )
Journal or Publication Title: Journal of Neurophysiology
Publisher: American Physiological Society
ISSN: 0022-3077
Official Date: 1 February 2015
Dates:
DateEvent
1 February 2015Published
12 November 2014Available
Date of first compliant deposit: 28 December 2015
Volume: 113
Number: 3
Page Range: pp. 871-882
DOI: 10.1152/jn.00620.2014
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item
twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us