Translational control by eIF2α kinases in long-lasting synaptic plasticity and long-term memory

Neurobiology of Learning and Memory

Volumn 105, Issue , 2013, Pages 93-99

  Trinh, Mimi A ^a   Klann, Eric ^b  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

^b NEW YORK UNIVERSITY   (United States)

Author keywords

GCN2; HRI; Knockout eIF2; Long term memory; PERK; PKR; Synaptic plasticity; Translation initiation

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; APOLIPOPROTEIN E; CCAAT ENHANCER BINDING PROTEIN ALPHA; CCAAT ENHANCER BINDING PROTEIN BETA; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; GAMMA INTERFERON; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 43; GUANINE NUCLEOTIDE EXCHANGE FACTOR; INITIATION FACTOR 2ALPHA; MESSENGER RNA; METHIONINE TRANSFER RNA; PROTEIN KINASE R; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

5' UNTRANSLATED REGION; ALZHEIMER DISEASE; ARTICLE; ATTENTION DEFICIT DISORDER; AUTISM; BIPOLAR DISORDER; COGNITION; COGNITIVE DEFECT; DISEASE ASSOCIATION; GENE OVEREXPRESSION; HIPPOCAMPAL CA1 REGION; HUMAN; INFORMATION PROCESSING; LEARNING; LONG TERM MEMORY; NERVE CELL; NERVE CELL PLASTICITY; NONHUMAN; OPEN READING FRAME; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; RNA TRANSLATION; SCHIZOPHRENIA; SPATIAL MEMORY; TRANSLATION REGULATION;

GCN2; HRI; KNOCKOUT EIF2; LONG-TERM MEMORY; PERK; PKR; SYNAPTIC PLASTICITY; TRANSLATION INITIATION;

ANIMALS; BRAIN; EIF-2 KINASE; EUKARYOTIC INITIATION FACTOR-2; HUMANS; MEMORY, LONG-TERM; MICE; NEURONAL PLASTICITY; PHOSPHORYLATION; PROTEIN BIOSYNTHESIS;

EID: 84884164633     PISSN: 10747427     EISSN: 10959564     Source Type: Journal    
DOI: 10.1016/j.nlm.2013.04.013     Document Type: Article

References (98)

1. Abel T., Martin K.C., Bartsch D., Kandel E.R. Memory suppressor genes: Inhibitory constraints on the storage of long-term memory. Science 1998, 279:338-341.
2. Baltzis D., Pluquet O., Papadakis A.I., Kazemi S., Qu L.K., Koromilas A.E. The eIF2alpha kinases PERK and PKR activate glycogen synthase kinase 3 to promote the proteasomal degradation of p53. Journal of Biological Chemistry 2007, 282:31675-31687.
3. Bando Y., Onuki R., Katayama T., Manabe T., Kudo T., Taira K., et al. Double-strand RNA dependent protein kinase (PKR) is involved in the extrastriatal degeneration in Parkinson's disease and Huntington's disease. Neurochemistry International 2005, 46:11-18.
4. Banko J.L., Hou L., Poulin F., Sonenberg N., Klann E. Regulation of eukaryotic initiation factor 4E by converging signaling pathways during metabotropic glutamate receptor-dependent long-term depression. Journal of Neuroscience 2006, 26:2167-2173.
5. Banko J.L., Poulin F., Hou L., DeMaria C.T., Sonenberg N., Klann E. The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus. Journal of Neuroscience 2005, 25:9581-9590.
6. Bartsch D., Ghirardi M., Skehel P.A., Karl K.A., Herder S.P., Chen M., et al. Aplysia CREB2 represses long-term facilitation: Relief of repression converts transient facilitation into long-term functional and structural change. Cell 1995, 83:979-992.
7. Bekinschtein P., Cammarota M., Katche C., Slipczuk L., Rossato J.I., Goldin A., et al. BDNF is essential to promote persistence of long-term memory storage. Proceedings of the National Academy of Sciences of the United States of America 2008, 105:2711-2716.
8. Ben-Asouli Y., Banai Y., Pel-Or Y., Shir A., Kaempfer R. Human interferon-gamma mRNA autoregulates its translation through a pseudoknot that activates the interferon-inducible protein kinase PKR. Cell 2002, 108:221-232.
9. Berlanga J.J., Santoyo J., De Haro C. Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2alpha kinase. European Journal of Biochemistry 1999, 265:754-762.
10. Bertolotti A., Zhang Y., Hendershot L.M., Harding H.P., Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nature Cell Biology 2000, 2:326-332.
11. Bingol B., Sheng M. Deconstruction for reconstruction: The role of proteolysis in neural plasticity and disease. Neuron 2011, 69:22-32.
12. Bitsios P., Giakoumaki S.G., Theou K., Frangou S. Increased prepulse inhibition of the acoustic startle response is associated with better strategy formation and execution times in healthy males. Neuropsychologia 2006, 44:2494-2499.
13. Bliss T.V., Collingridge G.L. A synaptic model of memory: Long-term potentiation in the hippocampus. Nature 1993, 361:31-39.
14. Bora E., Yucel M., Pantelis C. Cognitive endophenotypes of bipolar disorder: A meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. Journal of Affective Disorders 2009, 113:1-20.
15. Boyce M., Bryant K.F., Jousse C., Long K., Harding H.P., Scheuner D., et al. A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science 2005, 307:935-939.
16. Braff D.L., Geyer M.A., Light G.A., Sprock J., Perry W., Cadenhead K.S., et al. Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia. Schizophrenia Research 2001, 49:171-178.
17. Calkhoven C.F., Muller C., Leutz A. Translational control of C/EBPalpha and C/EBPbeta isoform expression. Genes & Development 2000, 14:1920-1932.
18. Carnevalli L.S., Pereira C.M., Jaqueta C.B., Alves V.S., Paiva V.N., Vattem K.M., et al. Phosphorylation of the alpha subunit of translation initiation factor-2 by PKR mediates protein synthesis inhibition in the mouse brain during status epilepticus. Biochemical Journal 2006, 397:187-194.
19. Carpick B.W., Graziano V., Schneider D., Maitra R.K., Lee X., Williams B.R. Characterization of the solution complex between the interferon-induced, double-stranded RNA-activated protein kinase and HIV-I trans-activating region RNA. Journal of Biological Chemistry 1997, 272:9510-9516.
20. Chen A., Muzzio I.A., Malleret G., Bartsch D., Verbitsky M., Pavlidis P., et al. Inducible enhancement of memory storage and synaptic plasticity in transgenic mice expressing an inhibitor of ATF4 (CREB-2) and C/EBP proteins. Neuron 2003, 39:655-669.
21. Cohen-Chalamish S., Hasson A., Weinberg D., Namer L.S., Banai Y., Osman F., et al. Dynamic refolding of IFN-gamma mRNA enables it to function as PKR activator and translation template. Nature Chemical Biology 2009, 5:896-903.
22. Connor J.H., Weiser D.C., Li S., Hallenbeck J.M., Shenolikar S. Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1. Molecular and Cellular Biology 2001, 21:6841-6850.
23. Costa-Mattioli M., Gobert D., Harding H., Herdy B., Azzi M., Bruno M., et al. Translational control of hippocampal synaptic plasticity and memory by the eIF2alpha kinase GCN2. Nature 2005, 436:1166-1173.
24. Costa-Mattioli M., Gobert D., Stern E., Gamache K., Colina R., Cuello C., et al. EIF2alpha phosphorylation bidirectionally regulates the switch from short- to long-term synaptic plasticity and memory. Cell 2007, 129:195-206.
25. Costa-Mattioli M., Sossin W.S., Klann E., Sonenberg N. Translational control of long-lasting synaptic plasticity and memory. Neuron 2009, 61:10-26.
26. Couturier J., Morel M., Pontcharraud R., Gontier V., Fauconneau B., Paccalin M., et al. Interaction of double-stranded RNA-dependent protein kinase (PKR) with the death receptor signaling pathway in amyloid beta (Abeta)-treated cells and in APPSLPS1 knock-in mice. Journal of Biological Chemistry 2010, 285:1272-1282.
27. Crino P.B., Eberwine J. Molecular characterization of the dendritic growth cone: Regulated mRNA transport and local protein synthesis. Neuron 1996, 17:1173-1187.
28. Crosby J.S., Lee K., London I.M., Chen J.J. Erythroid expression of the heme-regulated eIF-2 alpha kinase. Molecular and Cellular Biology 1994, 14:3906-3914.
29. Damjanac M., Page G., Ragot S., Laborie G., Gil R., Hugon J., et al. PKR, a cognitive decline biomarker, can regulate translation via two consecutive molecular targets p53 and Redd1 in lymphocytes of AD patients. Journal of Cellular and Molecular Medicine 2009, 13:1823-1832.
30. De Pietri Tonelli D., Mihailovich M., Di Cesare A., Codazzi F., Grohovaz F., Zacchetti D. Translational regulation of BACE-1 expression in neuronal and non-neuronal cells. Nucleic Acids Research 2004, 32:1808-1817.
31. Delepine M., Nicolino M., Barrett T., Golamaully M., Lathrop G.M., Julier C. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. Nature Genetics 2000, 25:406-409.
32. Deng J., Harding H.P., Raught B., Gingras A.C., Berlanga J.J., Scheuner D., et al. Activation of GCN2 in UV-irradiated cells inhibits translation. Current Biology 2002, 12:1279-1286.
33. Dever T.E., Dar A.C., Sicheri F. The eIF2α kinases. Translational control in biology and medicine 2007, 319-344. Cold Spring Harbor Laboratory Press, New York. N.S. Michael, B. Matthews, J.W.B. Hershey (Eds.).
34. Dey S., Baird T.D., Zhou D., Palam L.R., Spandau D.F., Wek R.C. Both transcriptional regulation and translational control of ATF4 are central to the integrated stress response. Journal of Biological Chemistry 2010, 285:33165-33174.
35. Dumurgier J., Mouton-Liger F., Lapalus P., Prevot M., Laplanche J.L., Hugon J., et al. Cerebrospinal fluid PKR level predicts cognitive decline in Alzheimer's disease. PLoS ONE 2013, 8:e53587.
36. Ehninger D., Han S., Shilyansky C., Zhou Y., Li W., Kwiatkowski D.J., et al. Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis. Nature Medicine 2008, 14:843-848.
37. Flexner J.B., Flexner L.B., Stellar E. Memory in mice as affected by intracerebral puromycin. Science 1963, 141:57-59.
38. Goos L.M., Crosbie J., Payne S., Schachar R. Validation and extension of the endophenotype model in ADHD patterns of inheritance in a family study of inhibitory control. American Journal of Psychiatry 2009, 166:711-717.
39. Harding H.P., Novoa I., Zhang Y., Zeng H., Wek R., Schapira M., et al. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Molecular Cell 2000, 6:1099-1108.
40. Harding H.P., Zeng H., Zhang Y., Jungries R., Chung P., Plesken H., et al. Diabetes mellitus and exocrine pancreatic dysfunction in perk-/- mice reveals a role for translational control in secretory cell survival. Molecular Cell 2001, 7:1153-1163.
41. Harding H.P., Zhang Y., Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 1999, 397:271-274.
42. Hinnebusch A.G. Translational regulation of GCN4 and the general amino acid control of yeast. Annual Review of Microbiology 2005, 59:407-450.
43. Hinnebusch A.G., Asano K., Olsen D.S., Phan L., Nielsen K.H., Valasek L. Study of translational control of eukaryotic gene expression using yeast. Annals of the New York Academy of Sciences 2004, 1038:60-74.
44. Hinnebusch A.G., Natarajan K. Gcn4p, a master regulator of gene expression, is controlled at multiple levels by diverse signals of starvation and stress. Eukaryotic Cell 2002, 1:22-32.
45. Hoglinger G.U., Melhem N.M., Dickson D.W., Sleiman P.M., Wang L.S., Klei L., et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nature Genetics 2011, 43:699-705.
46. Huber K.M., Kayser M.S., Bear M.F. Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression. Science 2000, 288:1254-1257.
47. Iacono M., Mignone F., Pesole G. UAUG and uORFs in human and rodent 5'untranslated mRNAs. Gene 2005, 349:97-105.
48. Jackson R.J., Hellen C.U., Pestova T.V. The mechanism of eukaryotic translation initiation and principles of its regulation. Nature Reviews Molecular Cell Biology 2010, 11:113-127.
49. Jiang Z., Belforte J.E., Lu Y., Yabe Y., Pickel J., Smith C.B., et al. EIF2alpha phosphorylation-dependent translation in CA1 pyramidal cells impairs hippocampal memory consolidation without affecting general translation. Journal of Neuroscience 2010, 30:2582-2594.
50. Jousse C., Oyadomari S., Novoa I., Lu P., Zhang Y., Harding H.P., et al. Inhibition of a constitutive translation initiation factor 2alpha phosphatase, CReP, promotes survival of stressed cells. Journal of Cell Biology 2003, 163:767-775.
51. Julier C., Nicolino M. Wolcott-Rallison syndrome. Orphanet J Rare Dis 2010, 5:29.
52. Kaang B.K., Choi J.H. Synaptic protein degradation in memory reorganization. Advances in Experimental Medicine and Biology 2012, 970:221-240.
53. Kandel E.R. The molecular biology of memory storage: A dialog between genes and synapses. Bioscience Reports 2001, 21:565-611.
54. Kang H., Schuman E.M. A requirement for local protein synthesis in neurotrophin-induced hippocampal synaptic plasticity. Science 1996, 273:1402-1406.
55. Kelleher R.J., Govindarajan A., Tonegawa S. Translational regulatory mechanisms in persistent forms of synaptic plasticity. Neuron 2004, 44:59-73.
56. Klann E., Sweatt J.D. Altered protein synthesis is a trigger for long-term memory formation. Neurobiology of Learning and Memory 2008, 89:247-259.
57. Lammich S., Schobel S., Zimmer A.K., Lichtenthaler S.F., Haass C. Expression of the Alzheimer protease BACE1 is suppressed via its 5'-untranslated region. EMBO Reports 2004, 5:620-625.
58. Lesh T.A., Niendam T.A., Minzenberg M.J., Carter C.S. Cognitive control deficits in schizophrenia: Mechanisms and meaning. Neuropsychopharmacology 2011, 36:316-338.
59. Ma Y., Hendershot L.M. Delineation of a negative feedback regulatory loop that controls protein translation during endoplasmic reticulum stress. Journal of Biological Chemistry 2003, 278:34864-34873.
60. Malenka R.C., Nicoll R.A. Long-term potentiation - A decade of progress?. Science 1999, 285:1870-1874.
61. Matsui M., Yachie N., Okada Y., Saito R., Tomita M. Bioinformatic analysis of post-transcriptional regulation by uORF in human and mouse. FEBS Letters 2007, 581:4184-4188.
62. McGaugh J.L. Memory - A century of consolidation. Science 2000, 287:248-251.
63. Mellor H., Flowers K.M., Kimball S.R., Jefferson L.S. Cloning and characterization of cDNA encoding rat hemin-sensitive initiation factor-2 alpha (eIF-2 alpha) kinase. Evidence for multitissue expression. Journal of Biological Chemistry 1994, 269:10201-10204.
64. Meurs E., Chong K., Galabru J., Thomas N.S., Kerr I.M., Williams B.R., et al. Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon. Cell 1990, 62:379-390.
65. Mignone F., Gissi C., Liuni S., Pesole G. Untranslated regions of mRNAs. Genome Biology 2002, 3. REVIEWS0004.
66. Neafsey D.E., Galagan J.E. Dual modes of natural selection on upstream open reading frames. Molecular Biology and Evolution 2007, 24:1744-1751.
67. Novoa I., Zeng H., Harding H.P., Ron D. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. Journal of Cell Biology 2001, 153:1011-1022.
68. Ozcan U., Ozcan L., Yilmaz E., Duvel K., Sahin M., Manning B.D., et al. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Molecular Cell 2008, 29:541-551.
69. Paquet C., Bose A., Polivka M., Peoc'h K., Brouland J.P., Keohane C., et al. Neuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease. Journal of Neuropathology and Experimental Neurology 2009, 68:190-198.
70. Patel R.C., Sen G.C. Requirement of PKR dimerization mediated by specific hydrophobic residues for its activation by double-stranded RNA and its antigrowth effects in yeast. Molecular and Cellular Biology 1998, 18:7009-7019.
71. Peel A.L., Bredesen D.E. Activation of the cell stress kinase PKR in Alzheimer's disease and human amyloid precursor protein transgenic mice. Neurobiology of Diseases 2003, 14:52-62.
72. Peel A.L., Rao R.V., Cottrell B.A., Hayden M.R., Ellerby L.M., Bredesen D.E. Double-stranded RNA-dependent protein kinase, PKR, binds preferentially to Huntington's disease (HD) transcripts and is activated in HD tissue. Human Molecular Genetics 2001, 10:1531-1538.
73. Pereira C.M., Sattlegger E., Jiang H.Y., Longo B.M., Jaqueta C.B., Hinnebusch A.G., et al. IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activation. Journal of Biological Chemistry 2005, 280:28316-28323.
74. Pestova T.V., Lorsh J.R., Hellen C.U.T. The mechanism of translation initiation in eukaryotes. Translational control in biology and medicine 2007, 87-128. Cold Spring Harbor Laboratory Press, New York. M.B. Mathews, N. Sonenberg, J.W.B. Hershey (Eds.).
75. Raven J.F., Baltzis D., Wang S., Mounir Z., Papadakis A.I., Gao H.Q., et al. PKR and PKR-like endoplasmic reticulum kinase induce the proteasome-dependent degradation of cyclin D1 via a mechanism requiring eukaryotic initiation factor 2alpha phosphorylation. Journal of Biological Chemistry 2008, 283:3097-3108.
76. Reis A.F., Kannengiesser C., Jennane F., Manna T.D., Cheurfa N., Oudin C., et al. Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome. Pediatric Diabetes 2011, 12:187-191.
77. Richter J.D., Klann E. Making synaptic plasticity and memory last: Mechanisms of translational regulation. Genes & Development 2009, 23:1-11.
78. Ron D., Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nature Reviews Molecular Cell Biology 2007, 8:519-529.
79. Rubio-Cabezas O., Patch A.M., Minton J.A., Flanagan S.E., Edghill E.L., Hussain K., et al. Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. Journal of Clinical Endocrinology and Metabolism 2009, 94:4162-4170.
80. Segev Y., Michaelson D.M., Rosenblum K. ApoE epsilon4 is associated with eIF2alpha phosphorylation and impaired learning in young mice. Neurobiology of Aging 2013, 34:863-872.
81. Senee V., Vattem K.M., Delepine M., Rainbow L.A., Haton C., Lecoq A., et al. Wolcott-Rallison syndrome: Clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity. Diabetes 2004, 53:1876-1883.
82. Shi Y., Vattem K.M., Sood R., An J., Liang J., Stramm L., et al. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Molecular and Cellular Biology 1998, 18:7499-7509.
83. Solomon M., Ozonoff S.J., Ursu S., Ravizza S., Cummings N., Ly S., et al. The neural substrates of cognitive control deficits in autism spectrum disorders. Neuropsychologia 2009, 47:2515-2526.
84. Sonenberg N., Dever T.E. Eukaryotic translation initiation factors and regulators. Current Opinion in Structural Biology 2003, 13:56-63.
85. Sood R., Porter A.C., Olsen D.A., Cavener D.R., Wek R.C. A mammalian homologue of GCN2 protein kinase important for translational control by phosphorylation of eukaryotic initiation factor-2alpha. Genetics 2000, 154:787-801.
86. Stern E., Chinnakkaruppan A., David O., Sonenberg N., Rosenblum K. Blocking the eIF2alpha kinase (PKR) enhances positive and negative forms of cortex-dependent taste memory. Journal of Neuroscience 2013, 33:2517-2525.
87. Steward O., Levy W.B. Preferential localization of polyribosomes under the base of dendritic spines in granule cells of the dentate gyrus. Journal of Neuroscience 1982, 2:284-291.
88. Tang S.J., Schuman E.M. Protein synthesis in the dendrite. Philosophical Transactions of the Royal Society of London. Series B, Biological sciences 2002, 357:521-529.
89. Thornton C.M., Carson D.J., Stewart F.J. Autopsy findings in the Wolcott-Rallison syndrome. Pediatric Pathology and Laboratory Medicine 1997, 17:487-496.
90. Trinh M.A., Kaphzan H., Wek R.C., Pierre P., Cavener D.R., Klann E. Brain-specific disruption of the eIF2alpha kinase PERK decreases ATF4 expression and impairs behavioral flexibility. Cell Reports 2012, 1:676-688.
91. Vattem K.M., Wek R.C. Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. Proceedings of the National Academy of Sciences of the United States of America 2004, 101:11269-11274.
92. Wei J., Sheng X., Feng D., McGrath B., Cavener D.R. PERK is essential for neonatal skeletal development to regulate osteoblast proliferation and differentiation. Journal of Cellular Physiology 2008, 217:693-707.
93. Wek R.C., Cavener D.R. Translational control and the unfolded protein response. Antioxidants & Redox Signaling 2007, 9:2357-2371.
94. Wek S.A., Zhu S., Wek R.C. The histidyl-tRNA synthetase-related sequence in the eIF-2 alpha protein kinase GCN2 interacts with tRNA and is required for activation in response to starvation for different amino acids. Molecular and Cellular Biology 1995, 15:4497-4506.
95. Zhang W., Feng D., Li Y., Iida K., McGrath B., Cavener D.R. PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasis. Cell Metabolism 2006, 4:491-497.
96. Zhang P., McGrath B., Li S., Frank A., Zambito F., Reinert J., et al. The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas. Molecular and Cellular Biology 2002, 22:3864-3874.
97. Zhang F., Romano P.R., Nagamura-Inoue T., Tian B., Dever T.E., Mathews M.B., et al. Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop. Journal of Biological Chemistry 2001, 276:24946-24958.
98. Zhu P.J., Huang W., Kalikulov D., Yoo J.W., Placzek A.N., Stoica L., et al. Suppression of PKR promotes network excitability and enhanced cognition by interferon-gamma-mediated disinhibition. Cell 2011, 147:1384-1396.