ノルアドレナリンによる恐怖学習・記憶調節の神経回路および分子メカニズム

2014 Fiscal Year Annual Research Report

• Project/Area Number: 13F03209
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: JOHANSEN JOSHUA 独立行政法人理化学研究所, 脳科学総合研究センター, チームリーダー (80625351)
• Co-Investigator(Kenkyū-buntansha): TAN Bao Zhen 独立行政法人理化学研究所, 脳科学総合研究センター, 外国人特別研究員
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: Fear / amygdala / CRTC1 / noradrenaline

Outline of Annual Research Achievements

Project 1: For these experiments we virally infected noradrenaline neurons in the locus coeruleus (LC) with archaerhodopsin-T (ArchT, a green light-activated outward proton pump used to inhibit neural activity) and used laser light to inactivate LC neuron terminals in the lateral amygdala (LA) during the unconditioned stimulus. Different adenoviral serotypes were injected to check for viral expression in the LC, and we tested various incubation times to verify terminal expression in the LA for light manipulation. Only the AAV/CAG-FLEX-GFP/ArchT vectors in serotype AAV9 infected LC neurons of TH-Cre rats robustly and at least 8 weeks of incubation was required for terminal expression. We used this approach to optogenetically inhibit locus coeruleus (LC) input terminals to the lateral amygdala (LA), a site of fear memory storage. Surprisingly this had no effect on fear conditioning, but expression of opsins in the LC terminals in LA was low and could explain this result.
Project 2: We examined whether CRTC1 translocation in LA neurons is necessary for fear learning. To do this we virally overexpressed a dominant negative form of CRTC1, which limits the transcriptional activity of CRTC1,or a short hairpin RNA (shRNA), to knockdown CRTC1, specifically in LA neurons. We found that viral knockdown or overexpression of a dominant negative form of CRTC1 impairs fear memory consolidation without affecting the initial learning. This was consistent with our previous results showing translocation of CRTC1 with fear learning.

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。