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Here, we report that the effect requires glutamate NMDA receptors and L-voltage\u2013dependent calcium channels and involves the activation of calcium\/calmodulin-dependent protein kinase II, in addition to both ribosomal and nonribosomal protein synthesis. All these mechanisms operate only when the proteasomal-ubiquitin protein degradation system is intact, which suggests that they depend on synaptic protein turnover. Extinction enhancement by novelty is of great potential importance in the treatment of fear memories, such as those of posttraumatic stress disorder; the treatments of choice for such conditions are based on extinction procedures.<\/jats:p>","DOI":"10.1073\/pnas.1400423111","type":"journal-article","created":{"date-parts":[[2014,3,3]],"date-time":"2014-03-03T21:26:27Z","timestamp":1393881987000},"page":"4572-4577","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":80,"title":["Hippocampal molecular mechanisms involved in the enhancement of fear extinction caused by exposure to novelty"],"prefix":"10.1073","volume":"111","author":[{"given":"Jociane","family":"de Carvalho Myskiw","sequence":"first","affiliation":[{"name":"National Institute of Translational Neuroscience, National Research Council of Brazil, and Memory Center, Brain Institute, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90610-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiane Regina Guerino","family":"Furini","sequence":"additional","affiliation":[{"name":"National Institute of Translational Neuroscience, National Research Council of Brazil, and Memory Center, Brain Institute, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90610-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Benetti","sequence":"additional","affiliation":[{"name":"National Institute of Translational Neuroscience, National Research Council of Brazil, and Memory Center, Brain Institute, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90610-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"National Institute of Translational Neuroscience, National Research Council of Brazil, and Memory Center, Brain Institute, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, 90610-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,3,3]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/385533a0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(97)01189-2"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/lm.89305"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2010.07.007"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1104495108"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2004.03.003"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1114198109"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2008.01.002"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1083-07.2007"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0907078106"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301642"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.09.001"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220875110"},{"key":"e_1_3_3_14_2","volume-title":"Conditioned Reflexes: An Investigation of the Physiological Activity of the Cerebral Cortex","author":"Pavlov IP","year":"1927","unstructured":"IP Pavlov, GV Anrep Conditioned Reflexes: An Investigation of the Physiological Activity of the Cerebral Cortex (Oxford Univ Press, London, 1927)."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/lm.34600"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2008.07.011"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2007.10.002"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1302356110"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.04.015"},{"key":"e_1_3_3_20_2","article-title":"Fear extinction can be made state-dependent on peripheral epinephrine: Role of norepinephrine in the nucleus tractus solitarius","author":"Rosa J","year":"2013","unstructured":"J Rosa, JC Myskiw, CR Furini, GG Sapiras, I Izquierdo, Fear extinction can be made state-dependent on peripheral epinephrine: Role of norepinephrine in the nucleus tractus solitarius. 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