Neuroscience

Fine-Tuning Neuronal Networks

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Science  06 Jan 2012:
Vol. 335, Issue 6064, pp. 15
DOI: 10.1126/science.335.6064.15-b

The double-stranded RNA-activated protein kinase (PKR) is widely present in vertebrates, and its activation leads to the phosphorylation of several substrates, the major known cytoplasmic target being the translation initiation factor eIF2α. PKR is activated in response to a variety of cellular stresses such as viral infection and status epilepticus, and in degenerating neurons in, among others, Huntington's, Parkinson's, Alzheimer's, and Creutzfeldt-Jakob's disease. At present, little is known about its role in normal neuronal function. Using transgenic mice, electrophysiology, immunohistochemistry, and behavioral analysis, Zhu et al. discovered that loss of PKR or pharmacological blockade of PKR activity in mice promoted hyperexcitability in cortical and hippocampal networks and enhanced long-lasting synaptic potentiation and long-term memory. PKR regulated these processes via selective control of GABAergic synaptic transmission mediated by interferon-γ (IFN-γ. These findings thus uncovered a new molecular signaling pathway that regulates network rhythmicity, synaptic plasticity, and memory storage in the adult brain. PKR is activated in various neuropathies and may therefore be a potential therapeutic target.

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