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Department of Biochemistry and Molecular Biology

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Dr. Chia-Lin Wu

Chia-Lin Wu

Appointment : Associate Professor

LabLearning and Memory Laboratory

Education : Ph.D.

University/NationTsing Hua Univ./Taiwan

Tel: 03-211-8800#5159

E-mail : clwu@mail.cgu.edu.tw

Research website : http://clwu88.wix.com/chialinwu-lab

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 three-hour 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).

Publications:

1.      Shih HW#, Wu CL#*, Chang SW, Liu TH, Lai SY, Fu TF, Fu CC, Chiang AS* (2015, Jul). Parallel circuits control temperature preference in Drosophila during aging. Nature Communications, 6: 7775; DOI: 10.1038/ncomms8775 (Impact factor=11.470; SCI, 3/57, MULTIDISCIPLINARY SCIENCES).(# co-first authors, * co-corresponding authors).

2.      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, Jun). PPL2ab neurons restore sexual responses in aged Drosophila males through dopamine. Nature Communications, 6: 7490; DOI: 10.1038/ncomms8490. (Impact factor=11.470; SCI, 3/57, MULTIDISCIPLINARY SCIENCES).(# co-first authors).

3.      Wu CL*, Fu TF, Chou YY, Yeh SR (2015, Mar). A single pair of neurons modulates egg-laying decisions in Drosophila. PLoS One, 10(3): e0121335. (Impact factor=3.234; SCI, 8/55, MULTIDISCIPLINARY SCIENCES) (* corresponding author).

4.      Wu CL, Shih MF M, Lee PT, Chiang AS* (2013, Dec). An octopamine-mushroom body circuit modulates the formation of anesthesia-resistant memory in Drosophila. Current Biology, 23: 2346-2354. (Impact factor=9.571; SCI, 15/290, BIOCHEMISTRY & MOLECULAR BIOLOGY).

5.      Wu TH, Lu YN, Chuang CL, Wu CL, Chiang AS, Krantz DE, Chang HY*. (2013, Mar). Loss of vesicular dopamine release precedes tauopathy in degenerative dopaminergic neurons in a Drosophila model expressing human tau. Acta Neuropathologica, 125: 711-725 (Impact factor=10.752; SCI, 4/192, CLINICAL NEUROLOGY).

6.      Kuo SY, Tu CH, Hsu YT, Wang HD, Wen RK, Lin CT, Wu CL, Huang YT, Huang GS, Lan TH, Fu TF* (2012, Dec). A hormone receptor-based transactivator bridges different binary systems to precisely control spatial-temporal gene expression in Drosophila. PLoS One, 7(12): e50855. (Impact factor=3.234; SCI, 9/57, MULTIDISCIPLINARY SCIENCES).

7.      Chen CC, Wu JK, Lin HW, Pai TP, Fu TF, Wu CL, Tully T, Chiang AS* (2012, Feb). Visualizing long-term memory formation in two neurons of Drosophila brain. Science, 335: 678-685. (Impact factor=33.611; SCI, 2/57, MULTIDISCIPLINARY SCIENCES).

8.      Wu CL, Shih MF M, Lai J SY, Yang HT, Turner CG, Chen L, Chiang AS*  (2011, May). Heterotypic gap junctions between two neurons in the Drosophila brain are critical for memory. Current Biology, 21: 848-854. (Impact factor=9.571; SCI, 15/290, BIOCHEMISTRY & MOLECULAR BIOLOGY).

9.      Chang YC, Hung WZ, Chang YC, Chang HC, Wu CL, Chiang AS*, Jackson GR, Sang TK (2011, Feb). 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. (Impact factor=7.528; SCI, 14/167, GENETICS & HEREDITY).

10.  Wu CL, Chiang AS* (2008, Nov). Genes and circuits for olfactory-associated long-term memory in Drosophila. Journal of Neurogenetics, 22: 257-284. (Impact factor=1.268; SCI, 221/252, NEUROSCIENCES).

11.  Wu CL, Xia S, Fu TF, Wang H, Chen YH, Leong D, Chiang AS*, Tully T (2007, Dec). Specific requirement of NMDA receptors for long-term memory consolidation in Drosophila ellipsoid body. Nature Neuroscience, 10(12): 1578-1586. (Impact factor=16.095; SCI, 5/252, NEUROSCIENCES).

12.  Xia S, Miyashita T, Fu TF, Lin WY, Wu CL, Pyzocha L, Lin IR, Saitoe M, Tully T, Chiang AS* (2005, Apr). NMDA receptors mediate olfactory learning and memory in Drosophila. Current Biology, 15603-615. (Impact factor=9.571; SCI, 15/290, BIOCHEMISTRY & MOLECULAR BIOLOGY).

 

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