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Mechanisms controlling expression and memory of emotions

開催日 2014/9/11
時間 14:00 - 16:00
会場 Room D(503)
Chairperson(s) 貝淵 弘三 / Kozo Kaibuchi (名古屋大学大学院医学系研究科 / Nagoya University Graduate School of Medicine, Japan)
南 雅文 / Masabumi Minami (北海道大学大学院薬学研究院薬理学研究室 / Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Japan)

Segregation of Anxiety and Fear by Two Parallel Septo-Habenular Pathways

  • S1-D-1-2
  • 山口 隆司 / Takashi Yamaguchi:1 壇上 輝子 / Teruko Danjo:1 Pastan Ira / Ira Pastan:2 疋田 貴俊 / Takatoshi Hikida:1 中西 重忠 / Shigetada Nakanishi:1 
  • 1:大阪バイオサイエンス研システムズ生物 / Dept Systems Biol, Osaka Bioscience Inst, Osaka, Japan 2:アメリカ国立がん研究所,アメリカ / National Cancer Institute, Bethesda, USA 

In the mammalian brain, the septum and the habenula are tightly interconnected and are thought to be a key linkage between the limbic forebrain and the midbrain. The septum is divided into the lateral, medial, and posterior septum and the posterior septum is further subdivided into the triangular septum (TS) and the bed nucleus of the anterior commissure (BAC). The habenula also forms a nuclear complex, which is subdivided into the lateral and medial habenula (LHb and MHb, respectively). Both the TS and BAC mainly project to the MHb and send their inputs to the midbrain raphe nuclei via the predominant innervation from the MHb to the interpeduncular nucleus (IPN). The interconnection of the TS/BAC with the MHb has been implicated in the control of emotional behaviors including anxiety and fear responses. However, because both the septum and habenula are organized as an assembly of multiple nuclei, the anatomical and functional linkages among the TS, BAC, and MHb has remained to be elucidated. To assess this question, we established a transgenic mouse model, in which the fusion protein of GFP and human interleukin-2 receptor (hIL-2R) was specifically expressed in the TS and BAC projection neurons to the MHb. Our investigation combined with anterograde and retrograde tracings, indicated the linkage between the TS/BAC and the MHb constitutes 2 parallel pathways composed of the TS-ventral MHb-core IPN and the BAC-dorsal MHb-peripheral IPN. The TS and BAC projection neurons were then selectively and separately ablated by immunotoxin-mediated cell targeting, in which the immunotoxin composed of the monoclonal hIL-2R antibody fused to bacterial toxin was microinjected into the targeted nuclei of transgenic mice. The selective elimination of the TS and BAC projection neurons differentially impaired anxiety-related and fear-directed responses, respectively. Our studies have thus demonstrated that not only the existence of distinct and parallel septo-habenular transmission pathways but also the segregated control of anxiety and fear responses by these parallel pathways.

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