Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell. 2011 Dec 9;147(6):1384-96. doi: 10.1016/j.cell.2011.11.029.

Suppression of PKR promotes network excitability and enhanced cognition by interferon-γ-mediated disinhibition.

Author information

  • 1Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

The double-stranded RNA-activated protein kinase (PKR) was originally identified as a sensor of virus infection, but its function in the brain remains unknown. Here, we report that the lack of PKR enhances learning and memory in several behavioral tasks while increasing network excitability. In addition, loss of PKR increases the late phase of long-lasting synaptic potentiation (L-LTP) in hippocampal slices. These effects are caused by an interferon-γ (IFN-γ)-mediated selective reduction in GABAergic synaptic action. Together, our results reveal that PKR finely tunes the network activity that must be maintained while storing a given episode during learning. Because PKR activity is altered in several neurological disorders, this kinase presents a promising new target for the treatment of cognitive dysfunction. As a first step in this direction, we show that a selective PKR inhibitor replicates the Pkr(-/-) phenotype in WT mice, enhancing long-term memory storage and L-LTP.

Copyright © 2011 Elsevier Inc. All rights reserved.

Comment in

PMID:
22153080
[PubMed - indexed for MEDLINE]
PMCID:
PMC3569515
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for PubMed Central
    Loading ...
    Write to the Help Desk