Graduate Institute of Biomedical Sciences

RESEARCH INTERESTS:

My research interest is to understand the neural circuits and molecular mechanisms

 contribute to memory. Drosophila melanogaster has contributed to this insight, fly can

 be taught to associate an odor, conditioned stimulus (CS), with a punitive foot shock,

 unconditioned stimulus (US). Fly memory can be genetically and behaviorally dissected into

 several different phases depending on the training protocols. In our prior studies, we

 have identified the NMDA receptors play the exclusive roles for different types of memory

 consolidation in Drosophila (Xia S et al., 2005 Current Biology, Wu CL et al., 2007 Nature

 Neuroscience, Wu CL et al., 2008, Journal of Neurogenetics).

   In our recent studies, we have revealed the gap junctions involved in specific type of

 intermediate-term memory formation. Gap junctions are important for normal brain functions

 but their contribution to memory has not been well characterized. We showed two modulatory

 neurons, i.e. the anterior paired lateral (APL) and dorsal paired medial (DPM) neurons,

 form gap-junctional communication in the mushroom body (MB), the learning and memory center

 in the Drosophila brain. Following disruption of such gap junctions with RNAi-mediated

 knockdowns of inx7 and inx6 in the APL and DPM neurons, respectively, we found that flies

 showed normal olfactory associative learning and intact Anesthesia-Resistant Memory (ARM)

 but could not form three-hour Anesthesia-Sensitive Memory (ASM). Our results indicate

 the heterotypic gap junctions between the APL and DPM neurons are an essential part of the

 MB circuitry for ASM, suggesting that a recurrent neural circuit, consisting of APL, DPM

 and MB neurons, may stabilize ASM inside the MB (Wu CL et al., 2011 Current Biology).

   More interestingly, we also found that chemical neurotransmission from the APL neuron

 is necessary for ARM consolidation rather than ASM. We identified the APL neurons are

 tyramine, Tβh, and octopamine immunopositive. Octopamine is the counterpart of human

 norepinephrine and may also play the role for memory formation. With an adult-stage-specific

 RNAi knockdown of Tβh in the APL neurons or Octβ2R octopamine receptors in the MB α’/β’

 Kenyon cells (KCs) impaired ARM. Our data imply octopamine released from the APL neurons

 acts on MB α’/β’ KCs via Octβ2R receptor to modulate Drosophila ARM formation. Together

 with previous findings suggest that two parallel ARM pathways, serotoninergic DPM-MB α/β

 KCs and octopaminergic APL-MB α’/β’ KCs, exist in the Drosophila brain (Wu CL et al.,

 2013 Current Biology).

發表論文：

Shyu WH, Lee WP, Chiang MH, Chang CC, Fu TF, Chiang HC, Wu T, Wu CL* (2019). Electrical synapses between mushroom body neurons are critical for consolidated memory retrieval in Drosophila. PLOS Genetics, doi: 10.1371/journal.pgen.1008153. (*corresponding author).

2.     Lien HM, Wu HY, Hung CL, Chen CJ, Wu CL, Chen KW, Huang CL, Chang SJ, Chen CC, Lin HJ*, Lai CH* (2019). Antibacterial activity of ovatodiolide isolated from Anisomeles indica against Helicobacter pylori. Scientific Reports, 9:4205/doi:10.1038/s41598-019-40735-y.

3.        Chen YA, Tzeng D TW, Huang YP, Lin CJ, Lo UG, Wu CL, Lin H, Hsieh JT, Tang CH*, Lai CH* (2018). Antrocin sensitizes prostate cancer cells to radiotherapy through inhibiting PI3K/AKT and MAPK signaling pathways. Cancers, 11: 34; doi:10.3390/cancer11010034.

4.        Wu CL*, Chang CC, Wu JK, Chiang MH, Yang CH, Chiang HC (2018). Mushroom body glycolysis is required for olfactory memory in Drosophila. Neurobiology of Learning and Memory, 150: 13-19. (*corresponding author).

5.        Chi KC, Tsai WC, Wu CL, Lin TY*, Hueng DY* (2018). An adult Drosophila glioma model for studying pathometabolic pathways of gliomagenesis. Molecular Neurobiology, doi: 10.1007/s12035-018-1392-2.

6.        Chen YA, Shih HW, Lin YC, Hsu HY, Wu TF, Tsai CH, Wu CL, Wu HY, Hsieh JT, Tang CH, Lai CH* (2018). Simvastatin sensitizes radioresistant prostate cancer cells by compromising DNA double-strand break repair. Frontiers in Pharmacology, 9: 600.

7.        Ji XR, Cheng KC, Chen YR, Lin TY, Cheung CHA, Wu CL, Chiang HC* (2018). Dysfunction of different cellular degeneration pathways contributes to specific β-amyloid42-induced pathologies. FASEB Journal, 32(3): 1375-1387.

8.        Shyu WH, Chiu TH, Chiang MH, Cheng YC, Tsai YL, Fu TF, Wu T, Wu CL* (2017). Neural circuits for long-term water-reward memory processing in thirsty Drosophila. Nature Communications, 8: 15230; doi: 10.1038/ncomms15230. (*corresponding author).

9.        Yang CN, Wu MF, Liu CC, Jung WH, Chang YC, Lee WP, Shiao YJ, Wu CL, Liou HH, Lin SK, Chan CC* (2017) Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia. Human Molecular Genetics, 26(20): 3909-3921.

10.    Chen SL, Chen YH, Wang CC, Yu YW, Tsai YC, Hsu HW, Wu CL, Wang PY, Chen LC, Lan TH*, Fu TF* (2017). Active and passive sexual roles that arise in Drosophila male-male courtship are modulated by dopamine levels in PPL2ab neurons. Scientific Reports, 7:44595/doi:10.1038/srep44595.

11.    Yang CH, Shih MF M, Chang CC, Chiang MH, Shih HW, Tsai YL, Chiang AS, Fu TF, Wu CL* (2016). Additive expression of consolidated memory through Drosophila mushroom body subsets. PLOS Genetics, 12(5): e1006061. (*corresponding author).

12.    Wu CL*, Fu TF, Chiang MH, Chang YW, Her JL, Wu T (2016). Magnetoreception regulates male courtship activity in Drosophila. PLOS One, 11(5): e0155942 (*corresponding author).      

13.    Shih HW#, Wu CL#*, Chang SW, Liu TH, Lai SY, Fu TF, Fu CC, Chiang AS* (2015). Parallel circuits control temperature preference in Drosophila during ageing. Nature Communications, 6: 7775; doi: 10.1038/ncomms8775. (#co-first authors, *co-corresponding authors).

14.    Kuo SY#, Wu CL#, Hsieh MY, Lin CT, Wen RK, Chen LC, Chen YH, Yu YW, Wang HD, Su YJ, Lin CJ, Yang CY, Guan HY, Wang PY, Lan TH*, Fu TF* (2015). PPL2ab neurons restore sexual responses in aged Drosophila males through dopamine. Nature Communications, 6: 7490; doi: 10.1038/ncomms8490. (#co-first authors).

15.    Wu CL*, Fu TF, Chou YY, Yeh SR (2015). A single pair of neurons modulates egg-laying decisions in Drosophila. PLoS One, 10(3): e0121335. (*corresponding author).

16.    Wu CL, Shih MF M, Lee PT, Chiang AS* (2013). An octopamine-mushroom body circuit modulates the formation of anesthesia-resistant memory in Drosophila. Current Biology, 23: 2346-2354.

17.    Wu TH, Lu YN, Chuang CL, Wu CL, Chiang AS, Krantz DE, Chang HY*. (2013). Loss of vesicular dopamine release precedes tauopathy in degenerative dopaminergic neurons in a Drosophila model expressing human tau. ACTA NEUROPATHOLOGICA, doi: 10.1007/s00401-013-1105-x.

18.    Kuo SY, Tu CH, Hsu YT, Wang HD, Wen RK, Lin CT, Wu CL, Huang YT, Huang GS, Lan TH, Fu TF* (2012). A hormone receptor-based transactivator bridges different binary systems to precisely control spatial-temporal gene expression in Drosophila. PLOS One, 7(12): e50855.

19.    Chen CC, Wu JK, Lin HW, Pai TP, Fu TF, Wu CL, Tully T, Chiang AS* (2012). Visualizing long-term memory formation in two neurons of Drosophila brain. Science, 335: 678-685.

20.    Wu CL, Shih MF M, Lai J SY, Yang HT, Turner CG, Chen L, Chiang AS* (2011). Heterotypic gap junctions between two neurons in the Drosophila brain are critical for memory. Current Biology, 21: 848-854.

21.    Chang YC, Hung WZ, Chang YC, Chang HC, Wu CL, Chiang AS, Jackson GR, Sang TK* (2011). Pathogenic VCP/TER94 alleles are dominant actives and contribute to neurodegeneration by altering cellular ATP level in a Drosophila IBMPFD model. PLOS Genetics, 7(2): e1001288.

22.    Wu CL, Chiang AS* (2008). Genes and circuits for olfactory-associated long-term memory in Drosophila. Journal of Neurogenetics, 22: 257-284.

23.    Wu CL, Xia S, Fu TF, Wang H, Chen YH, Leong D, Chiang AS*, Tully T* (2007). Specific requirement of NMDA receptors for long-term memory consolidation in Drosophila ellipsoid body. Nature Neuroscience, 10(12): 1578-1586.

24.    Xia S, Miyashita T, Fu TF, Lin WY, Wu CL, Pyzocha L, Lin IR, Saitoe M, Tully T, Chiang AS* (2005). NMDA receptors mediate olfactory learning and memory in Drosophila. Current Biology, 15: 603-615.

專書：

Shih MFM, Wu CL* (2017) Network functions and Plasticity—Gap Junction Underlying Labile Memory. ELSEVIER (*corresponding author).

研討會論文：

1.        Wu CL, Invited speaker. 2019 Asia-Pacific Drosophila Neurobiology Conference. January 16th-20th 2019, Taipei, Taiwan. Electrical synapses in Kenyon cells are critical for Drosophila olfactory memory.

2.        Wu CL, Invited speaker. The 13th Across the Taiwan Strait Symposium on Cell Biology. July 18th-22th 2018, Xining, China. Parallel brain circuits regulate long- and short-term memories in fruit fly.

3.        Wu CL, Invited speaker. EMBO Workshop on Neural Development. March 2nd-6rd 2018, Taipei, Taiwan. Water reward memory in Drosophila.

4.        Wu CL, Invited speaker. NPAS Symposium on Drosophila Neurobiology. July 26th 2017, Taipei, Taiwan. Water reward long-term memory in Drosophila.

5.        Wu CL, Invited speaker. The 16th Society of Chinese Bioscientists in America (SCBA) International Symposium; June 29 –July 3, 2017. Hangzhou, China. Synaptic Plasticity.

6.        Wu CL, Invited speaker. NCTS 2017 Challenges in Neuroscience. April 14, 2017, Hsinchu, Taiwan. Neural circuits for water reward long-term memory in Drosophila.

7.        Wu CL, Invited speaker. The 23th symposium on recent advances in cellular and Molecular Biology; Feb. 4-6, 2015. Kenting, Taiwan. Novel Technology: Brain circuits for consolidated memory in Drosophila.

8.        Wu CL, Invited speaker. SFN Neuroscience 2013; Nov. 9-13, 2013. San Diego, USA. Electrical coupling and microcircuits: Network operation and plasticity.

9.        Wu CL, Invited speaker. The 14th SCBA International Symposium; July. 18-22, 2013. Xi’an, China. The fly brain: Circuits and behavior.