4. German Humboldt Fellowship for Experienced Researchers
(2016/04/01)
5. "Newly Approved Integrated Research Grants in Health and
Medical Sciences" for 3 times (2016/05/25)
6. Young Scientist Award - TienTe Lee Biomedical Foundation
(2015/12/21)
7. NeuroCure Fellow of Charité – Universitätsmedizin Berlin
(2015/10/01)
8. DAAD Scholarship for the research visit at the Institute for
Physiology and Pathophysiology,Ruprecht-Karls-Universität
Heidelberg, Germany (2012)
9. German Academic Exchange Service (DAAD) scholarship
for PhD study (1998-2003)
10. Outstanding Educator Award from School of Medicine,
NYMU (2018/04, 2017/10, 2016/05, 2015/05, 2013/05,
2012/05, 2010/11, 2010/03, 2008/10) [PDF]
My lab is interested in understanding brain circuits and behavior in health and disease. More recently we have become increasingly interested in neural mechanisms underlying emotion and cognition. We mainly focus on two key regions in the limbic system, that is, the hippocampus and amygdala. To establish causal relationships between brain circuits and behavior, we combine the optogenetic or chemogenetic approach with different readout methodologies including electrophysiology and calcium imaging in freely moving animals. To uncover the input-output organization of the network, we employ optogenetics-assisted circuit mapping in brain slices maintained in vitro or in intact brains. Over the past decade, we have highlighted the relevance of GABAergic circuitry in both network and cognitive functions.
One of the grand challenges in brain research is to understand the wiring principle of the brain. Over the past decade, I mainly focused on three major topics:
First, what are the hierarchy, diversity and variability of central neurons?
Second, what is the cell type-specific expression pattern of channel/receptors in the brain and what is its physiological significance?
Third, how neurotransmission at central synapses is regulated and integrated along dendrites?
Mutidisciplinary approaches are currently used in my lab including: electrophysiology such as patch-clamp technique, fast calcium imaging, high-speed voltage imaging, two-photon imaging, single-cell RT-PCR, 3D morphological reconstruction, optogenetics, neuronal modeling, molecular biology, mouse genetics, animal behavioral study, etc.
1.
Wu PC, Fann MJ, Tran TT, Chen SC, Devina T, Cheng IH, Lien CC, Kao LS, Wang SJ, Fuh JL, Tzeng TT, Huang CY, Shiao YJ, Wong YH. Assessing the therapeutic potential of Graptopetalum paraguayense on Alzheimer's disease using patient iPSC-derived neurons. Sci Rep. 2019 Dec 17;9(1):19301. doi: 10.1038/s41598-019-55614-9. [PDF][PubMed]
2.
Hsu YT, Chang YG, Liu YC, Wang KY, Chen HM, Lee DJ, Yang SS, Tsai CH, Lien CC, Chern YJ. Enhanced Na+-K+-2Cl- cotransporter 1 underlies motor dysfunction in Huntington's disease. Mov Disord. 2019 Mar 6. [Epub ahead of print]. (Co-corresponding author) [PDF][PubMed]
3.
Chen CY, Di Lucente J, Lin YC, Lien CC, Rogawski MA, Maezawa I, Jin LW. Defective GABAergic neurotransmission in the nucleus tractus solitarius in Mecp2-null mice, a model of Rett syndrome. Neurobiol Dis 2018 Jan; 109(Pt A): 25-32. [PDF][PubMed]
4.
Martina M, Lien CC. (2018) Physiological Properties of Hippocampal Neurons. In: Cutsuridis V., Graham B., Cobb S., Vida I. (eds) Hippocampal Microcircuits. Springer Series in Computational Neuroscience. Springer, Cham. [PDF][Link]
5.
Huang CY, Lien CC, Cheng CF, Yen TY, Chen CJ, Tsaur ML. K+ channel Kv3.4 is essential for axon growth by limiting the influx of Ca2+ into growth cones. J Neurosci 2017 April; 37(17): 4433-4449. [PDF][PubMed]
6.
Kuo YL, Cheng JK, Hou WH, Chang YC, Du PH, Jian JJ, Rau RH, Yang JH, Lien CC, Tsaur ML. K+ channel modulatory subunits KChIP and DPP participate in Kv4-mediated mechanical pain control. J Neurosci 2017 April; 37(16): 4391-4404. [PDF][PubMed]
7.
Lee CT, Kao MH, Hou WH, Wei YT, Chen CL, Lien CC. Causal evidence for the role of specific GABAergic interneuron types in entorhinal recruitment of dentate granule cells. Sci Rep 2016 Nov; 6: 36885. (Corresponding author) [PDF][PubMed] [Supplementary Information]
8.
Wu CC, Lien CC, Hou WH, Chiang PM, Tsai KJ. Gain of BDNF function in engrafted neural stem cells promotes the therapeutic potential for Alzheimer's disease. Sci Rep 2016 Jun; 6: 27358. [PDF][PubMed]
9.
Hsu TT, Lee CT, Tai MH, Lien CC. Differential recruitment of dentate gyrus interneuron types by commissural versus perforant pathways. Cereb Cortex 2016 Jun; 26(6): 2715-27. (Corresponding author) [PDF][Supporting information][PebMed]
10.
Hou WH, Kuo N, Fang GW, Huang HS, Wu KP, Zimmer A, Cheng JK, Lien CC. Wiring Specificity and Synaptic Diversity in the Mouse Lateral Central Amygdala. J Neurosci 2016 April; 36(16): 4549-4563. (Corresponding author) (Featured Article)[PDF][PubMed]; also see Editor's Commentary [PDF][PDF (Chinese Ver.)]
11.
Chang CP, Lee CT, Hou WH, Lin MS, Lai HL, Chien CL, Chang C, Cheng PL, Lien CC*, Chern Y. Type VI adenylyl cyclase negatively regulates GluN2B-mediated LTD and spatial reversal learning. Sci Rep 2016 Mar; 6(22529): 1-16. (*co-corresponding author) [PDF][Supporting information][PebMed]
12.
Chiang PH, Chien TC, Chen CC, Yanagawa Y, Lien CC. ASIC-dependent LTP at multiple glutamatergic synapses in amygdala network is required for fear memory. Sci Rep 2015 May 19; 5: 10143. (Corresponding author) [PDF][Supporting information][PubMed]
13.
Lin SH, Chien YC, Chiang WW, Liu YZ, Lien CC, Chen CC.Genetic mapping of ASIC4 and contrasting phenotype to ASIC1a in modulating innate fear and anxiety. Eur J Neurosci 2015 Jun; 41(12): 1553-68.[PDF][PebMed]
14.
Chen WT, Hsieh YF, Huang YJ, Lin CC, Lin YT, Liu YC, Lien CC, Cheng IH. G206D mutation of Presenilin-1 reduces Pen2 interaction, increases Aβ42/Aβ40 ratio and elevates ER Ca2+ accumulation. Mol Neurobiol 2015 Dec; 52(3): 1835-49.[PebMed]
15.
Cheng CF, Cheng JK, Chen CY, Lien CC, Chu D, Wang SY, Tsaur ML. Mirror-image pain is mediated by NGF produced from TNFactivated satellite glia after peripheral nerve injury. Pain 2014 May; 155(5): 906-20.[PDF][Supporting information][PebMed]
16.
Liu YC, Cheng JK, Lien CC. Rapid dynamic changes of dendritic inhibition in the dentate gyrus by presynaptic activity patterns. J Neurosci 2014 Jan 22; 34(4): 1344-1357. (Corresponding author)[PDF][PebMed]
17.
Chan CF*, Kuo TW*, Weng JY*, Lin YC*, Chen TY*, Cheng JK, Lien CC. Ba2+- and bupivacaine-sensitive background K+ conductances mediate rapid EPSP attenuation in oligodendrocyte precursor cells.J Physiol (London) 2013 Oct 1; 591(19): 4843-58. *Co-First author (Corresponding author)[PDF][PebMed]
18.
Sun YY, Lin SH, Lin HC, Hung CC, Wang CY, Lin YC, Hung KS, Lien CC, Kuan CY, Lee YH. Cell type-specific denpendency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes. PLoS ONE 2013 Jul 9; 8(7): e69019. [PDF][Supporting information][PebMed]
19.
Wu PY, Huang YY, Chen CC, Hsu TT, Lin YC, Weng JY, Chien TC, Cheng H, Lien CC. Acid-sensing ion channel-1a is not required for normal hippocampal LTP and spatial memory. J Neurosci 2013 Jan; 33 (5): 1828-32. (Corresponding author) [PDF][PebMed]
20.
Lee YC, Alexandra D, Majczenko K, Huang YH,Liu YC, Lien CC, Tsai PC, Ichikawa Y, Goto J, Monin ML, Li JZ, Chung MY, Mundwiller E, Shakkottai V, Liu TT, Tesson C, Lu YC, Brice A, Tsuji S, Burmeister M, Stevanin G, Soong BW. Mutations in KCND3 cause spinocerebellar ataxia type 22. Ann Neurol 2012 Dec; 72 (6): 859-69.[PDF][Supporting Information][PebMed]
Chiang PH*, Wu PY*, Kuo TW*, Liu YC, Chan CF, Chien TC, Cheng JK, Huang YY, Chiu CD, Lien CC. GABA is depolarizing in hippocampal dentate granule cells of the adolescent and adult rats. J Neurosci 2012 Jan 4;32: 62-67. *Co-First author (Corresponding author)[PDF][PebMed]
23.
Lin YC, Liu YC, Huang YY, Lien CC. High-density expression of Ca2+-permeable ASIC1a channels in NG2 glia of rat hippocampus. PLoS ONE 2010 Sep 10; 5 (9): e12665-e12672. (Corresponding author)[PDF][PebMed]
24.
Chu KC, Chiu CD, Hsu TT, Hsieh YM, Huang YY, Lien CC. Functional identification of an outwardly rectifying pH- and anesthetic-sensitive leak K+ conductance in hippocampal astrocytes. Eur J Neurosci 2010 Jul 28; 32: 725-35. (Corresponding author)[PDF][Supporting Information][PebMed]
25.
Weng JY, Lin YC, Lien CC. Cell type-specific expression of acid-sensing ion channels in hippocampal interneurons.J Neurosci 2010 May 12; 30: 6548-58. (Corresponding author)[PDF][Supplementary Information][PebMed]
26.
Chiang PH, Yeh WC, Lee CT, Weng JY, Huang YY, Lien CC. M1-like muscarinic acetylcholine receptors regulate fast-spiking interneuron excitability in rat dentate gyrus. Neuroscience 2010 Aug 11; 169: 39-51. Epub 2010 Apr 28. (Corresponding author)[PDF][PebMed]
27.
Liao CW & Lien CC. Estimating intracellular Ca2+ concentrations and buffering in a dendritic inhibitory hippocampal interneuron. Neuroscience 2009 Dec 4; 164: 1701-11. (Corresponding author)[PDF][PebMed]
28.
Aponte Y, Lien CC, Jonas P. Hyperpolarization-activated cation channels in fast-spiking hippocampal interneurons.J Physiol (London) 2006 Jul 1; 574: 229-43.[PDF][PebMed]
29.
Lien CC, Mu Y, Vargas-Caballero M, Poo MM. Visual stimuli-induced LTD of GABAergic synapses mediated by presynaptic NMDA receptors. Nat Neurosci 2006 Mar; 9: 372-80.[PDF][Supplementary Information][PebMed]
30.
Oliver D*, Lien CC*, Soom M, Baukrowitz T, Jonas P, Fakler B. Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids. Science (Research Article) 2004 Apr 9; 304: 265-70. (*equal contribution)[PDF][Supporting Online Material][PebMed]
31.
Lien CC & Jonas P. Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons. J Neurosci 2003 Mar 15; 23: 2058-68.[PDF][PebMed]
32.
Lien CC, Martina M, Schultz J, Ehmke H, Jonas P. Gating, modulation, and subunit composition of voltage-gated K+channels in dendritic inhibitory interneurones of rat hippocampus. J Physiol (London) 2002 Jan 15; 538: 405-19.[PDF][PebMed]
