Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleCellular and Molecular

Regulation of GABAergic Inputs to CA1 Pyramidal Neurons by Nicotinic Receptors and Kynurenic Acid

Jyotirmoy Banerjee, Manickavasagom Alkondon, Edna F. R. Pereira and Edson X. Albuquerque
Journal of Pharmacology and Experimental Therapeutics May 2012, 341 (2) 500-509; DOI: https://doi.org/10.1124/jpet.111.189860
Jyotirmoy Banerjee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Manickavasagom Alkondon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edna F. R. Pereira
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edson X. Albuquerque
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Impaired α7 nicotinic acetylcholine receptor (nAChR) function and GABAergic transmission in the hippocampus and elevated brain levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the kynurenine pathway, are key features of schizophrenia. KYNA acts as a noncompetitive antagonist with respect to agonists at both α7 nAChRs and N-methyl-d-aspartate receptors. Here, we tested the hypothesis that in hippocampal slices tonically active α7 nAChRs control GABAergic transmission to CA1 pyramidal neurons and are sensitive to inhibition by rising levels of KYNA. The α7 nAChR-selective antagonist α-bungarotoxin (α-BGT; 100 nM) and methyllycaconitine (MLA; 10 nM), an antagonist at α7 and other nAChRs, reduced by 51.3 ± 1.3 and 65.2 ± 1.5%, respectively, the frequency of GABAergic postsynaptic currents (PSCs) recorded from CA1 pyramidal neurons. MLA had no effect on miniature GABAergic PSCs. Thus, GABAergic synaptic activity in CA1 pyramidal neurons is maintained, in part, by tonically active α7 nAChRs located on the preterminal region of axons and/or the somatodendritic region of interneurons that synapse onto the neurons under study. l-Kynurenine (20 or 200 μM) or KYNA (20–200 μM) suppressed concentration-dependently the frequency of GABAergic PSCs; the inhibitory effect of 20 μM l-kynurenine had an onset time of approximately 35 min and could not be detected in the presence of 100 nM α-BGT. These results suggest that KYNA levels generated from 20 μM kynurenine inhibit tonically active α7 nAChR-dependent GABAergic transmission to the pyramidal neurons. Disruption of nAChR-dependent GABAergic transmission by mildly elevated levels of KYNA can be an important determinant of the cognitive deficits presented by patients with schizophrenia.

Footnotes

  • This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant NS25296] (to E.X.A.).

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    http://dx.doi.org/10.1124/jpet.111.189860.

  • ABBREVIATIONS:

    nAChR
    nicotinic acetylcholine receptor
    α-BGT
    α- bungarotoxin
    ACSF
    artificial cerebrospinal fluid
    ANOVA
    analysis of variance
    APV
    2-amino-5-phosphonovaleric acid
    CNQX
    6-cyano-7-nitroquinoxaline-2,3-dione
    KAT II
    kynurenine aminotransferase II
    K-S
    Kolmogorov-Smirnov
    KYNA
    kynurenic acid
    MLA
    methyllycaconitine
    NMDA
    N-methyl-d-aspartate
    PSC
    postsynaptic current
    mPSC
    miniature PSC
    TTX
    tetrodotoxin
    QX-314
    N-(2,6-dimethylphenylcarbamoylmethyl) triethylammonium bromide
    τd
    decay-time constant.

  • Received November 8, 2011.
  • Accepted February 17, 2012.
  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 341 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 341, Issue 2
1 May 2012
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Regulation of GABAergic Inputs to CA1 Pyramidal Neurons by Nicotinic Receptors and Kynurenic Acid
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleCellular and Molecular

Kynurenic Acid Suppresses nAChR-Dependent GABA Release

Jyotirmoy Banerjee, Manickavasagom Alkondon, Edna F. R. Pereira and Edson X. Albuquerque
Journal of Pharmacology and Experimental Therapeutics May 1, 2012, 341 (2) 500-509; DOI: https://doi.org/10.1124/jpet.111.189860

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleCellular and Molecular

Kynurenic Acid Suppresses nAChR-Dependent GABA Release

Jyotirmoy Banerjee, Manickavasagom Alkondon, Edna F. R. Pereira and Edson X. Albuquerque
Journal of Pharmacology and Experimental Therapeutics May 1, 2012, 341 (2) 500-509; DOI: https://doi.org/10.1124/jpet.111.189860
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Chlorogenic Acid Inhibits Breast Cancer Metastasis
  • SNAP25 and mGluRs Control Pathological Tau Release
  • N-Stearoylethanolamine Inhibits Platelet Reactivity
Show more Cellular and Molecular

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics