研究生: |
陳俊朝 |
---|---|
論文名稱: |
透視果蠅長期記憶在兩顆腦神經細胞中之形成 Visualizing Long-Term Memory Formation in Two Neurons of the Drosophila Brain |
指導教授: | 江安世 |
口試委員: |
楊嘉鈴
張壯榮 孫以瀚 簡正鼎 |
學位類別: |
博士 Doctor |
系所名稱: |
生命科學暨醫學院 - 生物科技研究所 Biotechnology |
論文出版年: | 2013 |
畢業學年度: | 101 |
語文別: | 英文 |
論文頁數: | 69 |
中文關鍵詞: | Drosophila memory |
相關次數: | 點閱:2 下載:0 |
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摘要
長期記憶之形成需要新的蛋白質合成,我們透過使用溫度敏感型核糖體失活毒素蛋白準確抑制新蛋白質生成,來篩選果蠅腦中特定神經元,負責合成新蛋白並且儲存經過嗅覺關聯性學習後產生的長期記憶。意外發現抑制果蠅腦中的一對dorsal-anterior-lateral (DAL)神經元的新蛋白生成會使長期記憶損壞,而在一般認為是學習與記憶的中心的蕈狀體細胞中抑制新蛋白生成,則不影響長期記憶的形成。而經由使用光轉換變色螢光蛋白KAEDE來監測新生成的蛋白,我們在DAL神經元內直接觀察到受cyclic adenosine monophosphate (cAMP) response element–binding protein (CREB)調控下的calcium/calmodulin-dependent protein kinase II 與 period 二個基因基因轉錄活性增加,而這樣的現象只發生在果蠅經過可形成長期記憶間斷式的學習之後,而非無法形成長期記憶的連續性的學習過程之後。透過在記憶的讀取時阻斷抑制DAL神經細胞的傳導,會影響長期記憶,而在記憶的獲得或記憶的固化階段抑制則不影響長期記憶。這些發現支持在果蠅腦中存在有蕈狀體以外的記憶線路:長期記憶的固化(蕈狀體 DAL神經細胞),儲存記憶(DAL神經細胞)和提取記憶(DAL神經細胞蕈狀體)。
1. Akalal, D.B., Yu, D., and Davis, R.L. (2010). A late-phase, long-term memory trace forms in the gamma neurons of Drosophila mushroom bodies after olfactory classical conditioning. J Neurosci 30, 16699-16708.
2. Akalal, D.B., Yu, D., and Davis, R.L. (2011). The long-term memory trace formed in the Drosophila alpha/beta mushroom body neurons is abolished in long-term memory mutants. J Neurosci 31, 5643-5647.
3. Ando, R., Hama, H., Yamamoto-Hino, M., Mizuno, H., and Miyawaki, A. (2002). An optical marker based on the UV-induced green-to-red photoconversion of a fluorescent protein. Proceedings of the National Academy of Sciences of the United States of America 99, 12651-12656.
4. Ashraf, S.I., McLoon, A.L., Sclarsic, S.M., and Kunes, S. (2006). Synaptic protein synthesis associated with memory is regulated by the RISC pathway in Drosophila. Cell 124, 191-205.
5. Aso, Y., Siwanowicz, I., Bracker, L., Ito, K., Kitamoto, T., and Tanimoto, H. (2010). Specific dopaminergic neurons for the formation of labile aversive memory. Curr Biol 20, 1445-1451.
6. Belvin, M.P., Zhou, H., and Yin, J.C. (1999). The Drosophila dCREB2 gene affects the circadian clock. Neuron 22, 777-787.
7. Bolduc, F.V., Bell, K., Cox, H., Broadie, K.S., and Tully, T. (2008). Excess protein synthesis in Drosophila fragile X mutants impairs long-term memory. Nature neuroscience 11, 1143-1145.
8. Bourtchuladze, R., Frenguelli, B., Blendy, J., Cioffi, D., Schutz, G., and Silva, A.J. (1994). Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79, 59-68.
9. Chiang, A.S., Lin, C.Y., Chuang, C.C., Chang, H.M., Hsieh, C.H., Yeh, C.W., Shih, C.T., Wu, J.J., Wang, G.T., Chen, Y.C., et al. (2011). Three-dimensional reconstruction of brain-wide wiring networks in Drosophila at single-cell resolution. Curr Biol 21, 1-11.
10. Chiang, A.S., Liu, Y.C., Chiu, S.L., Hu, S.H., Huang, C.Y., and Hsieh, C.H. (2001). Three-dimensional mapping of brain neuropils in the cockroach, Diploptera punctata. The Journal of comparative neurology 440, 1-11.
11. Claridge-Chang, A., Roorda, R.D., Vrontou, E., Sjulson, L., Li, H., Hirsh, J., and Miesenbock, G. (2009). Writing memories with light-addressable reinforcement circuitry. Cell 139, 405-415.
12. Comas, D., Petit, F., and Preat, T. (2004). Drosophila long-term memory formation involves regulation of cathepsin activity. Nature 430, 460-463.
13. Davis, R.L. (2011). Traces of Drosophila memory. Neuron 70, 8-19.
14. Didelot, G., Molinari, F., Tchenio, P., Comas, D., Milhiet, E., Munnich, A., Colleaux, L., and Preat, T. (2006). Tequila, a neurotrypsin ortholog, regulates long-term memory formation in Drosophila. Science (New York, NY 313, 851-853.
15. Dubnau, J., Chiang, A.S., Grady, L., Barditch, J., Gossweiler, S., McNeil, J., Smith, P., Buldoc, F., Scott, R., Certa, U., et al. (2003). The staufen/pumilio pathway is involved in Drosophila long-term memory. Curr Biol 13, 286-296.
16. Dubnau, J., Grady, L., Kitamoto, T., and Tully, T. (2001). Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory. Nature 411, 476-480.
17. Endo, Y., Mitsui, K., Motizuki, M., and Tsurugi, K. (1987). The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and the characteristics of the modification in 28 S ribosomal RNA caused by the toxins. J Biol Chem 262, 5908-5912.
18. Endo, Y., and Tsurugi, K. (1987). RNA N-glycosidase activity of ricin A-chain. Mechanism of action of the toxic lectin ricin on eukaryotic ribosomes. J Biol Chem 262, 8128-8130.
19. Gerber, B., Tanimoto, H., and Heisenberg, M. (2004). An engram found? Evaluating the evidence from fruit flies. Current opinion in neurobiology 14, 737-744.
20. Gordon, M.D., and Scott, K. (2009). Motor control in a Drosophila taste circuit. Neuron 61, 373-384.
21. Hardin, P.E., Hall, J.C., and Rosbash, M. (1990). Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343, 536-540.
22. Heisenberg, M. (2003). Mushroom body memoir: from maps to models. Nature reviews 4, 266-275.
23. Isabel, G., Pascual, A., and Preat, T. (2004). Exclusive consolidated memory phases in Drosophila. Science (New York, NY 304, 1024-1027.
24. Keene, A.C., and Waddell, S. (2007). Drosophila olfactory memory: single genes to complex neural circuits. Nature reviews 8, 341-354.
25. Lin, H.H., Lai, J.S., Chin, A.L., Chen, Y.C., and Chiang, A.S. (2007). A map of olfactory representation in the Drosophila mushroom body. Cell 128, 1205-1217.
26. Liu, X., and Davis, R.L. (2009). The GABAergic anterior paired lateral neuron suppresses and is suppressed by olfactory learning. Nature neuroscience 12, 53-59.
27. Martinek, S., and Young, M.W. (2000). Specific genetic interference with behavioral rhythms in Drosophila by expression of inverted repeats. Genetics 156, 1717-1725.
28. McGuire, S.E., Le, P.T., and Davis, R.L. (2001). The role of Drosophila mushroom body signaling in olfactory memory. Science (New York, NY 293, 1330-1333.
29. McGuire, S.E., Le, P.T., Osborn, A.J., Matsumoto, K., and Davis, R.L. (2003). Spatiotemporal rescue of memory dysfunction in Drosophila. Science (New York, NY 302, 1765-1768.
30. Mizuno, H., Mal, T.K., Tong, K.I., Ando, R., Furuta, T., Ikura, M., and Miyawaki, A. (2003). Photo-induced peptide cleavage in the green-to-red conversion of a fluorescent protein. Molecular cell 12, 1051-1058.
31. Moffat, K.G., Gould, J.H., Smith, H.K., and O'Kane, C.J. (1992). Inducible cell ablation in Drosophila by cold-sensitive ricin A chain. Development (Cambridge, England) 114, 681-687.
32. Pascual, A., Huang, K.L., Neveu, J., and Preat, T. (2004). Neuroanatomy: brain asymmetry and long-term memory. Nature 427, 605-606.
33. Pascual, A., and Preat, T. (2001). Localization of long-term memory within the Drosophila mushroom body. Science (New York, NY 294, 1115-1117.
34. Pitman, J.L., Huetteroth, W., Burke, C.J., Krashes, M.J., Lai, S.L., Lee, T., and Waddell, S. (2011). A pair of inhibitory neurons are required to sustain labile memory in the Drosophila mushroom body. Curr Biol 21, 855-861.
35. Riemensperger, T., Voller, T., Stock, P., Buchner, E., and Fiala, A. (2005). Punishment prediction by dopaminergic neurons in Drosophila. Curr Biol 15, 1953-1960.
36. Sakai, T., Tamura, T., Kitamoto, T., and Kidokoro, Y. (2004). A clock gene, period, plays a key role in long-term memory formation in Drosophila. Proceedings of the National Academy of Sciences of the United States of America 101, 16058-16063.
37. Sejourne, J., Placais, P.Y., Aso, Y., Siwanowicz, I., Trannoy, S., Thoma, V., Tedjakumala, S.R., Rubin, G.M., Tchenio, P., Ito, K., et al. (2011). Mushroom body efferent neurons responsible for aversive olfactory memory retrieval in Drosophila. Nature neuroscience 14, 903-910.
38. Tully, T., Preat, T., Boynton, S.C., and Del Vecchio, M. (1994). Genetic dissection of consolidated memory in Drosophila. Cell 79, 35-47.
39. Tully, T., and Quinn, W.G. (1985). Classical conditioning and retention in normal and mutant Drosophila melanogaster. J Comp Physiol 157, 263-277.
40. Wu, C.L., Shih, M.F., Lai, J.S., Yang, H.T., Turner, G.C., Chen, L., and Chiang, A.S. (2011). Heterotypic gap junctions between two neurons in the Drosophila brain are critical for memory. Curr Biol 21, 848-854.
41. Wu, C.L., Xia, S., Fu, T.F., Wang, H., Chen, Y.H., Leong, D., Chiang, A.S., and Tully, T. (2007). Specific requirement of NMDA receptors for long-term memory consolidation in Drosophila ellipsoid body. Nature neuroscience 10, 1578-1586.
42. Xia, S., Miyashita, T., Fu, T.F., Lin, W.Y., Wu, C.L., Pyzocha, L., Lin, I.R., Saitoe, M., Tully, T., and Chiang, A.S. (2005). NMDA receptors mediate olfactory learning and memory in Drosophila. Curr Biol 15, 603-615.
43. Yin, J.C., Wallach, J.S., Del Vecchio, M., Wilder, E.L., Zhou, H., Quinn, W.G., and Tully, T. (1994). Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell 79, 49-58.
44. Yu, D., Akalal, D.B., and Davis, R.L. (2006). Drosophila alpha/beta mushroom body neurons form a branch-specific, long-term cellular memory trace after spaced olfactory conditioning. Neuron 52, 845-855.