Radwanska Kasia, Schenatto-Pereira Grace, Ziółkowska Magdalena, Łukasiewicz Kacper, Giese K Peter
Laboratory of Molecular Basis of Behavior, Nencki Institute, ul. L. Pasteura 3, Warsaw, Poland; Centre for the Cellular Basis of Behavior, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London, James Black Centre, 125 Coldharbour Lane, London SE5 8AF, UK.
Centre for the Cellular Basis of Behavior, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London, James Black Centre, 125 Coldharbour Lane, London SE5 8AF, UK; Núcleo de Neurociências (NNC), Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, Belo Horizonte, Minas Gerais, Brazil.
Neurobiol Learn Mem. 2015 Nov;125:106-12. doi: 10.1016/j.nlm.2015.08.007. Epub 2015 Aug 28.
Understanding the molecular and cellular process specifically regulated during fear memory consolidation and extinction is a critical step toward development of new strategies in the treatment of human fear disorders. Here we used inhibitory component of AP-1 transcription factor, JunB, in order to map brain regions where JunB-dependent transcription is regulated during consolidation and extinction of contextual fear memory. We found that contextual fear memory consolidation induced JunB expression in the medial nucleus and intercalated cells of the amygdala while extinction training induced JunB in the CA1 and CA3 areas of the dorsal hippocampus. JunB upregulation induced by contextual fear memory extinction was absent in alphaCaMKII autophosphorylation-deficient mice which have impaired contextual fear memory extinction. Thus, our data suggest that JunB expression in the medial nucleus and intercalated cells of the amygdala is involved in fear memory consolidation while alphaCaMKII-autophosphorylation-dependent JunB expression in the areas CA1 and CA3 of the dorsal hippocampus regulates fear memory extinction.
了解在恐惧记忆巩固和消退过程中受到特异性调控的分子和细胞过程，是开发治疗人类恐惧障碍新策略的关键一步。在此，我们利用AP-1转录因子的抑制成分JunB，来确定在情境恐惧记忆的巩固和消退过程中，JunB依赖性转录受到调控的脑区。我们发现，情境恐惧记忆巩固诱导杏仁核内侧核和插入细胞中JunB表达，而消退训练则诱导背侧海马体CA1和CA3区中JunB表达。在情境恐惧记忆消退受损的αCaMKII自磷酸化缺陷小鼠中，情境恐惧记忆消退诱导的JunB上调不存在。因此，我们的数据表明，杏仁核内侧核和插入细胞中的JunB表达参与恐惧记忆巩固，而背侧海马体CA1和CA3区中αCaMKII自磷酸化依赖性JunB表达调节恐惧记忆消退。
