91猫先生

研究经歷及研究方向

研究方向

Our research interests focus on the information processing by mammalian brain circuits.  The brain function is based on interconnected neurons (i.e. the neural networks) capable of carrying and transmitting electrical signals or rhythms (i.e. the neural “codes”).  Work in our laboratory seeks to decode the brain by dissecting normal and deranged brain rhythms with an across-level approach, from molecules to circuits to behaviors.  To this end, several functional network research systems have been established and investigated in depth in the present laboratory.  These include the cortico-basal ganglia networks responsible for central motor control and symptomatic pathogenesis of Parkinson’s disease, the cortico-thalamic networks for sensorimotor processing, vigilance, and cognition, and the cortico-amygdalar networks for cognition and epileptogenesis. The cortico-subcortical reentrant loops form the main circuitries that generate mammalian brain rhythms.  Brain rhythms necessarily would be correlated with neural activities, which must play a determinant role in behavior and cognition, although the underlying mechanisms remain largely unclear.  In recent years, we have endeavored to uncover novel unifying principles underlying brain rhythmogenesis in physiological as well as pathophysiological (epileptic or parkinsonian) conditions.

脑主要藉由产生各种电讯息(电码)及其变化，来执行各式功能。调整电码，可能改变功能。

近年光电磁先进技术及数位科技等的蓬勃进展，人们开始期待藉由结合这些先进科技来调整脑功能及治疗脑疾病。但主要瓶颈仍在生物端。也就是脑如何产生电码、如何传讯、及其所代表的意义和功能為何等等，仍存在着太多未解之谜。

我们的研究兴趣，即在探究「神经系统电讯息处理原则及其对功能影响」。我们的主要研究策略為，在纵深上，努力开发由分子、细胞、突触、迴路至功能行為之各种实验方法及研究角度；在广度上，期待归纳不同神经网路系统运作的共同新原则或新观念，并深入探究不同系统如何演绎此些原则，以执行各系统之特定功能。期待藉由这些努力，能扩展我们对脑神经网路放电发生机制、讯息处理原则、对功能影响及疾病下异常变化之了解，并或能获致相关临床疾病创新疗法之机会。

為了執行上述研究目標，我們目前已在长庚大学建立數個哺乳動物腦神經迴路研究模式系統。主要有三大方向。一為負責感覺處理、意識及醒睡調控相關迴路系統(腦皮質-視丘迴路研究系統)，一為负责运动规划及与巴金森氏病病态生理相关之迴路系统(脑皮质-基底核迴路研究系统)，另一為负责情绪、认知及癲癇发生相关之迴路系统(脑皮质-边缘系统迴路研究系统)。我们过去的研究中，探索了神经讯号传递之基本元素-电位控制型离子通道及神经传递物质控制型离子通道之分子运作机制与其调节(分子及细胞层次)。并研究突触传递、突触可塑性及迴路活动的生理与机制，以及神经修饰物质或临床药物对其之调节作用(突触及迴路层次)。同时将结果与动物甚至临床病人之脑电活动及行為做关联及验证(活体层次)。

近期系列研究，由基本的放电元件、细胞放电、细胞间电码传讯和变化、神经网路讯息处理及功能输出等多重研究角度切入，对导致巴金森氏症运动障碍以及癲癇症等，主要中枢神经疾病之关键病态电码，及其矫治，有了突破性的发现及解析。哺乳动物的认知和感觉运动统合等是奠基於脑网路的神经运算，此运算需仰赖持续自动的节律性放电。此节律性放电為何能产生，是神经生物学上长久未解之重大谜团。我们近期进一步发现了，脑得以持续节律性放电之关键分子机制，即动态电突触。此建构了过去未被发现的新的大脑独特的可塑性机制。亦首次提供了将结构变化(即藉由动态分子造成的实质网路组件)转译為脑电气波动的学理基础。其结果為学习、记忆、灵感、决策、甚至癲癇发生及其他脑律疾病等之发生机制，提供了前所未有的全新观念。这些研究结果共同指出，藉由在基础学理上的突破，以进而精準有效矫治“脑律不整”，是脑科学研究及脑疾病治疗之极重要新思维方向。

我们希望藉着持续努力，能由分子至系统，由机制至功能，对神经生理甚至神经疾病有更通透之解析，并為神经生物学上的诸多有趣问题提供一些解答。

NEW! 發現大腦可塑性的新形式及腦永無休止活動之關鍵--动态电突触
Dynamic electrical synapses for a new form of plasticity and relentless activities of the brain



研究相关奖励荣誉

2022,2023  指導醫師獲 長庚醫院住院醫師優良論文獎第一名
2019起    科技部「台灣腦科技發展及國際躍升計畫」整合型計畫補助
2019      指導博士生獲 李天德醫藥科技獎 傑出論文獎
2018      指導醫學生獲 臺灣醫學發展基金會論文獎 特優獎
2018      指導碩士生獲 長庚生醫所壁報論文競賽 優選
2012      共同第一作者論文獲 有庠科技論文獎
2012      指導碩士生獲 長庚生醫所壁報論文競賽 優選
2010起   屢獲科技部獎勵特殊優秀人才補助
2007      台北醫學大學研究論文獎
2004      台大醫學院博士生論文傑出獎

论文与着作

近期论文选列：&苍产蝉辫;
(皆通讯作者论文)
Selected Recent Publications:
(Y.-C. Yang serves as the Corresponding Author for all papers listed below)

1.          Y.-C. Yang, G.-H. Wang, P. Chou, S.-W. Hsueh, Y.-C. Lai, C.-C. Kuo. Dynamic electrical synapses rewire brain networks for persistent oscillations and epileptogenesis.  Proceedings of the National Academy of Sciences of the United States of America (2024) 121(8):e2313042121

2.          G.-H. Wang, A.-Y. Chuang, Y.-C. Lai, H.-I. Chen, S.-W. Hsueh, Y.-C. Yang. Pre- and post-synaptic A-type K+ channels regulate glutamatergic transmission and switching of the network into epileptiform oscillations.  British Journal of Pharmacology (2022) 179(14):3754– 3777

3.          L.-H. N. Lee, C.-S. Huang, R.-W. Wang, H.-J. Lai, C.-C. Chung, Y.-C. Yang, C.-C. Kuo. Deep brain stimulation rectifies the noisy cortex and irresponsive subthalamus to improve parkinsonian locomotor activities.  npj Parkinsons Disease (2022) 8:77 

4.          C.-S. Huang, G.-H. Wang, H.-H. Chuang, A.-Y. Chuang, J.-Y. Yeh, Y.-C. Lai, Y.-C. Yang. Conveyance of cortical pacing for parkinsonian tremor-like hyperkinetic behavior by subthalamic dysrhythmia. Cell Reports (2021) 35:109007

5.          Y.-C. Lin, Y.-C. Lai, P. Chou, S.-W. Hsueh, T.-H. Lin, C.-S. Huang, R.-W. Wang, Y.-C. Yang, C.-C. Kuo. How can a Na+ channel inhibitor ameliorate seizures in Lennox-Gastaut syndrome? Annals of Neurology (2021) 89(6): 1099-1113

6.          Y.-C. Yang, G.‐H. Wang, A.‐Y. Chuang, S.‐W. Hsueh. Perampanel reduces paroxysmal depolarizing shift and inhibitory synaptic input in excitatory neurons to inhibit epileptic network oscillations. British Journal of Pharmacology (2020) 177(22):5177-5194

7.          G.-H. Wang, P. Chou, S.-W. Hsueh, Y.-C. Yang, C.-C. Kuo. Glutamate transmission rather than cellular pacemaking propels excitatory-inhibitory resonance for ictogenesis in amygdala. Neurobiology of Disease (2020) 148:105188

8.          P. Chou, G.-H. Wang, S.-W. Hsueh, Y.-C. Yang, C.-C. Kuo. Delta-frequency augmentation and synchronization in seizure discharges and telencephalic transmission. iScience (2020) 23(11):101666 

9.          Y.-S. Chen, Y.-C. Tu, Y.-C. Lai, Erin Liu, Y.-C. Yang, C.-C. Kuo. Desensitization of NMDA channels requires ligand binding to both GluN1 and GluN2 subunits to constrict the pore beside the activation gate. Journal of Neurochemistry (2019) 153:549–566

10.      C.-S. Huang, G.-H. Wang, C.-H. Tai, C.-C. Hu, Y.-C. Yang. Antiarrhythmics cure brain arrhythmia: the imperativeness of subthalamic ERG K+ channels in parkinsonian discharges. Science Advances (2017) 3:e1602272

11.      Y.-C. Yang, Hu C-C and Lai Y-C. Non-additive modulation of synaptic transmission by serotonin, adenosine,and cholinergic modulators in the sensory thalamus. Frontiers in Cellular Neuroscience (2015) 9:60.

12.      Y.-C. Yang, C.-C. Hu, C.-S. Huang, and P.-Y. Chou. Thalamic synaptic transmission of sensory information modulated by synergistic interaction of adenosine and serotonin. Journal of Neurochemistry (2014) 128:852-863

13.      C.-H. Tai, M.-K. Pan, J. J. Lin, C.-S. Huang, Y.-C. Yang and C.-C. Kuo Subthalamic discharges as a causal determinant of parkinsonian motor deficits. Annals of Neurology (2012) 72(3):464-76.