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.
journal_name
Celljournal_title
Cellauthors
Zhu PJ,Huang W,Kalikulov D,Yoo JW,Placzek AN,Stoica L,Zhou H,Bell JC,Friedlander MJ,Krnjević K,Noebels JL,Costa-Mattioli Mdoi
10.1016/j.cell.2011.11.029subject
Has Abstractpub_date
2011-12-09 00:00:00pages
1384-96issue
6eissn
0092-8674issn
1097-4172pii
S0092-8674(11)01375-4journal_volume
147pub_type
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