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

Cortical oscillatory dynamics and benzodiazepine-site modulation of tonic inhibition in fast spiking interneurons

Tools
- Tools
+ Tools

Prokic, Emma J., Weston, Cathryn, Yamawaki, Naoki , Hall, Stephen D., Jones, Roland S. G., Stanford, Ian M., Ladds, Graham and Woodhall, Gavin L. (2015) Cortical oscillatory dynamics and benzodiazepine-site modulation of tonic inhibition in fast spiking interneurons. Neuropharmacology, 95 . pp. 192-205. doi:10.1016/j.neuropharm.2015.03.006 ISSN 0028-3908.

[img]
Preview
PDF
WRAP_1-s2.0-S0028390815000982-main.pdf - Published Version - Requires a PDF viewer.
Available under License Creative Commons Attribution 4.0.

Download (2766Kb) | Preview
Official URL: http://dx.doi.org/10.1016/j.neuropharm.2015.03.006

Request Changes to record.

Abstract

Tonic conductance mediated by extrasynaptic GABAA receptors has been implicated in the modulation of network oscillatory activity. Using an in vitro brain slice to produce oscillatory activity and a kinetic model of GABAA receptor dynamics, we show that changes in tonic inhibitory input to fast spiking interneurons underlie benzodiazepine-site mediated modulation of neuronal network synchrony in rat primary motor cortex. We found that low concentrations (10 nM) of the benzodiazepine site agonist, zolpidem, reduced the power of pharmacologically-induced beta-frequency (15–30 Hz) oscillatory activity. By contrast, higher doses augmented beta power. Application of the antagonist, flumazenil, also increased beta power suggesting endogenous modulation of the benzodiazepine binding site. Voltage-clamp experiments revealed that pharmacologically-induced rhythmic inhibitory postsynaptic currents were reduced by 10 nM zolpidem, suggesting an action on inhibitory interneurons. Further voltage clamp studies of fast spiking cells showed that 10 nM zolpidem augmented a tonic inhibitory GABAA receptor mediated current in fast spiking cells whilst higher concentrations of zolpidem reduced the tonic current. A kinetic model of zolpidem-sensitive GABAA receptors suggested that incubation with 10 nM zolpidem resulted in a high proportion of GABAA receptors locked in a kinetically slow desensitized state whilst 30 nM zolpidem favoured rapid transition into and out of desensitized states. This was confirmed experimentally using a challenge with saturating concentrations of GABA. Selective modulation of an interneuron-specific tonic current may underlie the reversal of cognitive and motor deficits afforded by low-dose zolpidem in neuropathological states.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Interneurons, Motor cortex
Journal or Publication Title: Neuropharmacology
Publisher: Elsevier
ISSN: 0028-3908
Official Date: August 2015
Dates:
DateEvent
August 2015Published
20 March 2015Available
8 March 2015Accepted
9 February 2014Updated
25 November 2014Submitted
Volume: 95
Number of Pages: 14
Page Range: pp. 192-205
DOI: 10.1016/j.neuropharm.2015.03.006
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 28 July 2016
Date of first compliant Open Access: 28 July 2016
Funder: Warwick Impact Fund, University of Warwick Research Development Fund, Birmingham Science City, Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC)
Grant number: BB/ G01227X/1 (BBSRC)

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

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