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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 閔明源(Ming-Yuan Min) | |
dc.contributor.author | Rui-Ni Wu | en |
dc.contributor.author | 吳芮妮 | zh_TW |
dc.date.accessioned | 2021-06-15T12:30:54Z | - |
dc.date.available | 2019-08-24 | |
dc.date.copyright | 2016-08-24 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-04 | |
dc.identifier.citation | Ahn, N.G., and Krebs, E. (1990). Evidence for an epidermal growth factor-stimulated protein kinase cascade in Swiss 3T3 cells. Activation of serine peptide kinase activity by myelin basic protein kinases in vitro. Journal of Biological Chemistry 265, 11495-11501.
Aston-Jones, G., and Bloom, F. (1981a). Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. The Journal of Neuroscience 1, 876-886. Aston-Jones, G., and Bloom, F. (1981b). Nonrepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli. The journal of neuroscience 1, 887-900. Bangasser, D.A., Curtis, A., Reyes, B.A., Bethea, T.T., Parastatidis, I., Ischiropoulos, H., Van Bockstaele, E.J., and Valentino, R.J. (2010). Sex differences in corticotropin-releasing factor receptor signaling and trafficking: potential role in female vulnerability to stress-related psychopathology. Molecular psychiatry 15, 896-904. Bangasser, D.A., Zhang, X., Garachh, V., Hanhauser, E., and Valentino, R.J. (2011). Sexual dimorphism in locus coeruleus dendritic morphology: a structural basis for sex differences in emotional arousal. Physiology & behavior 103, 342-351. Ben‐Ari, Y., Cherubini, E., Corradetti, R., and Gaiarsa, J. (1989). Giant synaptic potentials in immature rat CA3 hippocampal neurones. The Journal of physiology 416, 303-325. Berridge, C.W., and Waterhouse, B.D. (2003). The locus coeruleus–noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Research Reviews 42, 33-84. Burger, P.M., Hell, J., Mehl, E., Krasel, C., Lottspeich, F., and Jahn, R. (1991). GABA and glycine in synaptic vesicles: storage and transport characteristics. Neuron 7, 287-293. Callado, L.F., and Stamford, J.A. (2000). Spatiotemporal Interaction of α2 Autoreceptors and Noradrenaline Transporters in the Rat Locus Coeruleus. Journal of neurochemistry 74, 2350-2358. Cedarbaum, J.M., and Aghajanian, G.K. (1978). Afferent projections to the rat locus coeruleus as determined by a retrograde tracing technique. Journal of Comparative Neurology 178, 1-15. Christie, M., Williams, J., and North, R. (1989). Electrical coupling synchronizes subthreshold activity in locus coeruleus neurons in vitro from neonatal rats. The Journal of Neuroscience 9, 3584-3589. Couve, A., Thomas, P., Calver, A.R., Hirst, W.D., Pangalos, M.N., Walsh, F.S., Smart, T.G., and Moss, S.J. (2002). Cyclic AMP–dependent protein kinase phosphorylation facilitates GABAB receptor–effector coupling. Nature neuroscience 5, 415-424. Dimitrov, E.L., Yanagawa, Y., and Usdin, T.B. (2013). Forebrain GABAergic projections to locus coeruleus in mouse. Journal of Comparative Neurology 521, 2373-2397. Drolet, G., Van Bockstaele, E.J., and Aston-Jones, G. (1992). Robust enkephalin innervation of the locus coeruleus from the rostral medulla. The Journal of neuroscience 12, 3162-3174. Ennis, M., and Aston-Jones, G. (1989). GABA-mediated inhibition of locus coeruleus from the dorsomedial rostral medulla. The Journal of neuroscience 9, 2973-2981. Ennis, M., Behbehani, M., Shipley, M.T., van Bockstaele, E.J., and Aston‐Jones, G. (1991). Projections from the periaqueductal gray to the rostromedial pericoerulear region and nucleus locus coeruleus: anatomic and physiologic studies. Journal of comparative neurology 306, 480-494. Fairfax, B.P., Pitcher, J.A., Scott, M.G., Calver, A.R., Pangalos, M.N., Moss, S.J., and Couve, A. (2004). Phosphorylation and chronic agonist treatment atypically modulate GABAB receptor cell surface stability. Journal of Biological Chemistry 279, 12565-12573. Foote, S., Aston-Jones, G., and Bloom, F. (1980). Impulse activity of locus coeruleus neurons in awake rats and monkeys is a function of sensory stimulation and arousal. Proceedings of the National Academy of Sciences 77, 3033-3037. Foote, S.L., Bloom, F.E., and Aston-Jones, G. (1983). Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiological reviews 63, 844-914. Gaiarsa, J.L., McLean, H., Congar, P., Leinekugel, X., Khazipov, R., Tseeb, V., and Ben‐Ari, Y. (1995). Postnatal maturation of gamma‐aminobutyric acidA and B‐mediated inhibition in the CA3 hippocampal region of the rat. Journal of neurobiology 26, 339-349. Grampp, T., Notz, V., Broll, I., Fischer, N., and Benke, D. (2008). Constitutive, agonist-accelerated, recycling and lysosomal degradation of GABA B receptors in cortical neurons. Molecular and Cellular Neuroscience 39, 628-637. Grampp, T., Sauter, K., Markovic, B., and Benke, D. (2007). γ-Aminobutyric acid type B receptors are constitutively internalized via the clathrin-dependent pathway and targeted to lysosomes for degradation. Journal of Biological Chemistry 282, 24157-24165. Guitart, X., Thompson, M.A., Mirante, C.K., Greenberg, M.E., and Nestler, E.J. (1992). Regulation of cyclic AMP response element‐binding protein (CREB) phosphorylation by acute and chronic morphine in the rat locus coeruleus. Journal of neurochemistry 58, 1168-1171. Hagan, J.J., Leslie, R.A., Patel, S., Evans, M.L., Wattam, T.A., Holmes, S., Benham, C.D., Taylor, S.G., Routledge, C., and Hemmati, P. (1999). Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proceedings of the National Academy of Sciences 96, 10911-10916. Hill, D. (1985). GABAB receptor modulation of adenylate cyclase activity in rat brain slices. British journal of pharmacology 84, 249. Hobson, J.A., McCarley, R.W., and Wyzinski, P.W. (1975). Sleep cycle oscillation: reciprocal discharge by two brainstem neuronal groups. Science 189, 55-58. Hoshi, M., Nishida, E., and Sakai, H. (1988). Activation of a Ca2+-inhibitable protein kinase that phosphorylates microtubule-associated protein 2 in vitro by growth factors, phorbol esters, and serum in quiescent cultured human fibroblasts. Journal of Biological Chemistry 263, 5396-5401. Ishimatsu, M., and Williams, J.T. (1996). Synchronous activity in locus coeruleus results from dendritic interactions in pericoerulear regions. The Journal of neuroscience 16, 5196-5204. Ji, R.-R., Befort, K., Brenner, G.J., and Woolf, C.J. (2002). ERK MAP kinase activation in superficial spinal cord neurons induces prodynorphin and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity. The Journal of neuroscience 22, 478-485. Kaupmann, K., Malitschek, B., Schuler, V., Heid, J., Froestl, W., Beck, P., Mosbacher, J., Bischoff, S., Kulik, A., and Shigemoto, R. (1998). GABAB-receptor subtypes assemble into functional heteromeric complexes. Nature 396, 683-687. Kawasaki, Y., Kohno, T., Zhuang, Z.-Y., Brenner, G.J., Wang, H., Van Der Meer, C., Befort, K., Woolf, C.J., and Ji, R.-R. (2004). Ionotropic and metabotropic receptors, protein kinase A, protein kinase C, and Src contribute to C-fiber-induced ERK activation and cAMP response element-binding protein phosphorylation in dorsal horn neurons, leading to central sensitization. The Journal of neuroscience 24, 8310-8321. Lüscher, C., Jan, L.Y., Stoffel, M., Malenka, R.C., and Nicoll, R.A. (1997). G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. Neuron 19, 687-695. Leroy, D., Missotten, M., Waltzinger, C., Martin, T., and Scheer, A. (2007). G protein-coupled receptor-mediated ERK1/2 phosphorylation: towards a generic sensor of GPCR activation. Journal of Receptors and Signal Transduction 27, 83-97. Margeta-Mitrovic, M., Jan, Y.N., and Jan, L.Y. (2000). A trafficking checkpoint controls GABA B receptor heterodimerization. Neuron 27, 97-106. Marshall, F.H., Jones, K.A., Kaupmann, K., and Bettler, B. (1999). 7TM heterodimers. McCall, J.G., Al-Hasani, R., Siuda, E.R., Hong, D.Y., Norris, A.J., Ford, C.P., and Bruchas, M.R. (2015). CRH engagement of the locus coeruleus noradrenergic system mediates stress-induced anxiety. Neuron 87, 605-620. Mintz, I.M., and Bean, B.P. (1993). GABA B receptor inhibition of P-type Ca 2+ channels in central neurons. Neuron 10, 889-898. Moore, R., and Bloom, F. (1978). Central catecholamine neuron systems: anatomy and physiology of the dopamine systems. Annual review of neuroscience 1, 129-169. Moore, R., and Bloom, F. (1979). Central catecholamine neuron systems: anatomy and physiology of the norepinephrine and epinephrine systems. Annual review of neuroscience 2, 113-168. Mugnaini, E., and Oertel, W.H. (1985). An atlas of the distribution of GABAergic neurons and terminals in the rat CNS as revealed by GAD immunohistochemistry. Handbook of chemical neuroanatomy 4, 436-608. Nitz, D., and Siegel, J.M. (1997). GABA release in the locus coeruleus as a function of sleep/wake state. Neuroscience 78, 795-801. Paradiso, M.A., Bear, M.F., and Connors, B.W. (2007). Neuroscience: exploring the brain. Hagerstwon, MD: Lippincott Williams & Wilkins, 718. Poncer, J.-C., McKinney, R.A., Gähwiler, B.H., and Thompson, S.M. (1997). Either N-or P-type calcium channels mediate GABA release at distinct hippocampal inhibitory synapses. Neuron 18, 463-472. Posada, J., and Cooper, J.A. (1992). Requirements for phosphorylation of MAP kinase during meiosis in Xenopus oocytes. Science 255, 212-215. Rampon, C., Peyron, C., Gervasoni, D., Pow, D.V., Luppi, P.H., and Fort, P. (1999). Origins of the glycinergic inputs to the rat locus coeruleus and dorsal raphe nuclei: a study combining retrograde tracing with glycine immunohistochemistry. European Journal of Neuroscience 11, 1058-1066. Rasmussen, K., and Aghajanian, G.K. (1989). Withdrawal-induced activation of locus coeruleus neurons in opiate-dependent rats: attenuation by lesions of the nucleus paragigantocellularis. Brain research 505, 346-350. Rasmussen, K., Beitner-Johnson, D.B., Krystal, J.H., Aghajanian, G.K., and Nestler, E.J. (1990). Opiate withdrawal and the rat locus coeruleus: behavioral, electrophysiological, and biochemical correlates. The Journal of Neuroscience 10, 2308-2317. Ritter, B., and Zhang, W. (2000). Early postnatal maturation of GABAA‐mediated inhibition in the brainstem respiratory rhythm‐generating network of the mouse. European Journal of Neuroscience 12, 2975-2984. SALLESE, M., SALVATORE, L., D’URBANO, E., SALA, G., STORTO, M., LAUNEY, T., NICOLETTI, F., KNÖPFEL, T., and DE BLASI, A. (2000). The G-protein-coupled receptor kinase GRK4 mediates homologous desensitization of metabotropic glutamate receptor 1. The FASEB Journal 14, 2569-2580. Saper, C.B., Chou, T.C., and Scammell, T.E. (2001). The sleep switch: hypothalamic control of sleep and wakefulness. Trends in neurosciences 24, 726-731. Sapin, E., Lapray, D., Bérod, A., Goutagny, R., Léger, L., Ravassard, P., Clément, O., Hanriot, L., Fort, P., and Luppi, P.-H. (2009). Localization of the brainstem GABAergic neurons controlling paradoxical (REM) sleep. PLoS One 4, e4272. Schwenk, J., Metz, M., Zolles, G., Turecek, R., Fritzius, T., Bildl, W., Tarusawa, E., Kulik, A., Unger, A., and Ivankova, K. (2010). Native GABAB receptors are heteromultimers with a family of auxiliary subunits. Nature 465, 231-235. Shimizu, K., Asano, M., Kitagawa, J., Ogiso, B., Ren, K., Oki, H., Matsumoto, M., and Iwata, K. (2006). Phosphorylation of extracellular signal-regulated kinase in medullary and upper cervical cord neurons following noxious tooth pulp stimulation. Brain research 1072, 99-109. Somogyi, J., and Llewellyn‐Smith, I. (2001). Patterns of colocalization of GABA, glutamate and glycine immunoreactivities in terminals that synapse on dendrites of noradrenergic neurons in rat locus coeruleus. European Journal of Neuroscience 14, 219-228. Soya, S., Shoji, H., Hasegawa, E., Hondo, M., Miyakawa, T., Yanagisawa, M., Mieda, M., and Sakurai, T. (2013). Orexin receptor-1 in the locus coeruleus plays an important role in cue-dependent fear memory consolidation. The Journal of Neuroscience 33, 14549-14557. Strahlendorf, H.K., Strahlendorf, J.C., and Barnes, C.D. (1980). Endorphin-mediated inhibition of locus coeruleus neurons. Brain Research 191, 284-288. Sweatt, J.D. (2001). The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. Journal of neurochemistry 76, 1-10. Thuault, S.J., Brown, J.T., Sheardown, S.A., Jourdain, S., Fairfax, B., Spencer, J.P., Restituito, S., Nation, J.H., Topps, S., and Medhurst, A.D. (2004). The GABA B2 subunit is critical for the trafficking and function of native GABA B receptors. Biochemical pharmacology 68, 1655-1666. Tu, H., Rondard, P., Xu, C., Bertaso, F., Cao, F., Zhang, X., Pin, J.P., and Liu, J. (2007). Dominant role of GABAB2 and Gbetagamma for GABAB receptor-mediated-ERK1/2/CREB pathway in cerebellar neurons. Cell Signal 19, 1996-2002. Van Bockstaele, E., Bajic, D., Proudfit, H., and Valentino, R. (2001). Topographic architecture of stress-related pathways targeting the noradrenergic locus coeruleus. Physiology & behavior 73, 273-283. Van Bockstaele, E., Reyes, B., and Valentino, R. (2010). The locus coeruleus: a key nucleus where stress and opioids intersect to mediate vulnerability to opiate abuse. Brain research 1314, 162-174. Van Bockstaele, E.J., Peoples, J., and Valentino, R.J. (1999). Anatomic basis for differential regulation of the rostrolateral peri–locus coeruleus region by limbic afferents. Biological psychiatry 46, 1352-1363. Vanhoose, A.M., Emery, M., Jimenez, L., and Winder, D.G. (2002). ERK activation by G-protein-coupled receptors in mouse brain is receptor identity-specific. J Biol Chem 277, 9049-9053. Virlon, B., Firsov, D., Cheval, L., Reiter, E., Troispoux, C., Guillou, F., and Elalouf, J.-M. (1998). Rat G Protein-Coupled Receptor Kinase GRK4: Identification, Functional Expression, and Differential Tissue Distribution of Two Splice Variants 1. Endocrinology 139, 2784-2795. Wang, H.Y., Kuo, Z.C., Fu, Y.S., Chen, R.F., Min, M.Y., and Yang, H.W. (2015). GABAB receptor‐mediated tonic inhibition regulates the spontaneous firing of locus coeruleus neurons in developing rats and in citalopram‐treated rats. The Journal of physiology 593, 161-180. Watabe, A.M., Zaki, P.A., and O'Dell, T.J. (2000). Coactivation of β-adrenergic and cholinergic receptors enhances the induction of long-term potentiation and synergistically activates mitogen-activated protein kinase in the hippocampal CA1 region. The Journal of Neuroscience 20, 5924-5931. Williams, J., and Marshall, K. (1987). Membrane properties and adrenergic responses in locus coeruleus neurons of young rats. The Journal of neuroscience 7, 3687-3694. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50147 | - |
dc.description.abstract | 藍斑核(LC)-正腎上腺素性神經元在中樞神經系統中扮演著許多重要的生理功能,包括情緒、鎮痛以及睡眠清醒週期等。在實驗室前人的研究顯示,藍斑核神經元的自發性放射動作電位是受到伽瑪-胺基丁酸B型受器 (GABABR) 所調控。然而,對於藍斑核神經元中GABABR的調控機制尚不明瞭。
代謝型GABABR調控在眾多大腦神經活性並且扮演重要功能,它在突觸前及突觸後神經元皆有表現,透過抑制電位依賴型鈣離子通道與開啟鉀離子通道抑制神經活性。除此之外,我們發現活化的GABABR能夠誘導胞外信號調節激酶(ERK1/2)的表現,ERK1/2也被認為是調控正腎上腺素性神經元以改變動物行為的角色之一。 本研究採用全細胞膜片箝制紀錄、細胞接觸型紀錄、細胞組織免疫化學呈色法及西方點墨法,以此探討伽瑪-胺基丁酸B型受器-胞外信號調節激酶途徑在藍斑核細胞上的調控機制。型態上的結果發現在藍斑核細胞中磷酸化的ERK1/2信號表現具有生理節律週期,此節律近似於藍斑核胞外的GABA濃度變化週期,也和藍斑核的活性變化節律相反•我們將藍斑核組織從處理過GABABR激活劑巴氯芬(baclofen)的腦幹切片分離出來,接著使用西方點墨法偵測蛋白表現,結果發現磷酸化的ERK1及ERK2表現量上升。此外,巴氯芬造成磷酸化的ERK1/2的增加效果,可以被GABABR抑制劑 (CGP54626)給去除。有趣的是,在全細胞紀錄下,給予藍斑核巴氯芬誘導出一電流,電流波形顯示此電流具有緩慢且部分去敏感化的特性。將腦切片預先給予ERK1/2抑制劑 (U0126 or FR180204)而不是ERK1抑制劑(PD98059)處理,巴氯芬誘導的電流波形顯示更快速且顯著的去敏感化特性。除了去敏感化之外,G蛋白偶合受體的膜上膜內運輸也是控制GABABR重要因素之一。使用細胞接觸型紀錄發現ERK1/2的活性也會影響GABABR回送到藍斑核細胞膜上的運輸,更進一步改變藍斑核的放射動作電位頻率。 綜合以上結果顯示GABABR的活化激發ERK1/2信號途徑並且自我調控,以延緩GABABR的去敏感化且能夠回復藍斑核細胞膜上的GABABR。因此GABABR的持續性抑制效果能夠維持且穩定藍斑核的放射動作電位頻率。 | zh_TW |
dc.description.abstract | Locus Coeruleus (LC)-noradrenaline system plays important roles in many brain functions, including decision making, arousal, emotion, antinociception and sleep-wake cycle. The previous data of our group showed that the spontaneous firing rate (SFR) of LC neurons is regulated by GABAB receptors (GABABRs) in a tonic inhibition manner. However, the mechanism of this GABABR regulation is still unknown.
The metabotropic GABAB receptor (GABABR) plays important roles in regulating neuronal excitability in the brain. GABABR is well known to exert both pre- and postsynaptic inhibition through inhibiting voltage-gated Ca2+ channel and activating K+ (GIRK) channel, respectively. Beside these effects, here we found that GABABR activation caused an increase in phosphorylated extracellular signal- regulated kinase 1/2 (pERK1/2) level in LC, which consists of noradrenergic neurons and play divers roles in behavior. Our work applies whole cell patch-clamp and cell-attachment electrophysiology, cellular immunohistochemistry staining and western blot to study the GABABR-pERK1/2 signaling pathway mechanism on LC neurons in rats. Morphological results show that pERK1/2 signal in LC neurons exhibits circadian cycle which is similar to ambient GABA level, opposite to LC activity. Using western-blot analysis, LC tissues isolated from brainstem slices bathed in baclofen, a GABABR agonist, showed an increase in pERK1 and pERK2 compared to tissue from slices bathed in normal medium. Furthermore, this effect was specific to GABABR activation as it was not observed in LC tissue from slices bathed with baclofen and CGP54626, a GABABR antagonist. More interestingly, in whole cell recording, bath application of baclofen for 15 min induced a CGP54626 sensitive baclofen-induced current in LC neuron (Vm -70 mV) that underwent slow and partial desensitization. In slices pretreated with ERK1/2 blockers, U0126 or FR180204, but not in ERK1 blocker, PD98059, baclofen-induced current showed a faster and more prominent desensitization. Besides to desensitization, balance of GPCR trafficking is also important for controlling the GABAB receptor functions. Using cell-attachment recording, we found that ERK1/2 activity is involved in restoration of GABAB receptor on cell surface of LC neurons, and further affects the average firing rate of LC neurons. Together, the above results show that GABABR activation recruits ERK1/2-signaling pathway for an autoregulation that prevents GABABR from quick desensitization and restores cell surface GABABR of LC neurons, therefore maintains tonic inhibition, an important mechanism for tuning FR of LC neurons. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T12:30:54Z (GMT). No. of bitstreams: 1 ntu-105-R02b21014-1.pdf: 2813639 bytes, checksum: d5e1b80aef84519d0285a59e356fdb9f (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 口試委員審定書 i
誌謝 ii 摘要 iii ABSTRACT v CONTENTS vii Introduction 1 1 Locus coeruleus and Norepinephrine 1 1.1 NE-catecholamine transmitter family 1 1.1.1 Catecholamine synthesis 1 1.1.2 Variable function of NE 2 1.1.3 LC-NE system 3 1.2 The Locus Coeruleus 4 1.2.1 Name and Discovery 4 1.2.2 Anatomy of LC 4 1.2.3 Abundant transmitter afferent from limited area 5 1.2.4 Discharge pattern of LC 6 1.3 Circuity of LC 8 1.3.1 Basic property of LC neuron 8 1.3.2 Transmitter innervation of LC 9 1.4 Behavior and LC 11 1.4.1 Arousal and sleep cycle 11 1.4.2 Pain regulation 12 1.4.3 Stress and aversion 13 1.4.4 Opioid withdrawal 14 2 GABAergic regulation on LC 15 2.1 GABAergic regulation 15 2.1.1 GABA as transmitter 15 2.1.2 GABA receptor 15 2.1.3 Depolarizing GABA responses in early postnatal state 17 2.2 GABAB receptor 17 2.3 Inhibitory inputs to LC neurons 18 3 Extracellular Signal-Regulated Kinases on LC 19 3.1 ERK signaling and function 19 3.2 G protein-dependent ERK activation 20 3.3 Possible function of pERK1/2 on LC 21 4 Specific aims 21 Materials and Methods 22 Animals 22 Slice preparation for electrophysiology and western blot 22 Electrophysiology 23 Filling of recorded neurons with biocytin and immunohischemistry 24 Western blot analysis 25 Surgery and microinjection 26 Immunohistochemistry and immunofluorescence 28 Drug 29 Data analysis 30 Results ……… 31 1 Identification and recording of LC NAergic neurons 31 1.1 Morphological characterization of KC NAergic neurons in rat brainstem slice 31 1.2 Electrical membrane properties of LC neurons 31 2 LC NAergic neurons highly expressed GABAB receptors 32 3 LC NAergic neurons expressed pERK1/2 33 3.1 LC NAergic neurons expressed pERK1/2 33 3.2 Expression of pERK1/2 during daytime is higher than night in mouse LC neurons 34 4 The activation of GABAB receptor increases the ERK1/2 phosphorylation in LC neurons 35 4.1 Baclofen induced GABAB receptor-dependent pERK1/2 protein expression in LC neurons 35 4.2 Baclofen cannot increase pERK1/2 expression in living animals LC neurons 36 5 Function of GABAB receptor in LC neurons 37 5.1 GABAB receptor provides long-lasting standing potward current, which is pERK1/2-dependent 37 5.2 ERK functions in GABAB receptors trafficking balance of LC neurons 38 Discussion..… 41 The relationship between phospho-ERK1/2 expression and ambient GABA levels on LC neurons 42 Activation of GABAB receptor induced phosphorylation of ERK1/2 42 Microinjection baclofen cannot induce pERK1/2 expression 43 ERK1/2 blockers, U0126 and FR180204, but not PD98059, can interfere the trafficking balance of GABAB receptor 45 Acknowledgments 47 References 47 Figures 60 Fig. 1. Morphological identification of LC neurons 60 Fig. 2. Electrical identification of LC neurons in the current- and the voltage-clamp recording 62 Fig. 3. Expression of GABAB receptor in LC neurons 64 Fig. 4. Expression of phospho-ERK1/2 in LC neurons 66 Fig. 5. Expression of phospho-ERK1/2 in LC neurons during daytime and night period 68 Fig. 6. Baclofen application induced ERK1/2 phosphorylation on LC nuclei 70 Fig. 7. Baclofen cannot increase ERK1/2 phosphorylation in living animal LC neurons 72 Fig. 8. Effect of ERK1/2 blockers on the baclofen induced current and GABAB receptor desensitization 74 Fig. 9. Effect of ERK1/2 blockers on the desensitization and restoration of GABAB receptor 77 | |
dc.language.iso | en | |
dc.title | 伽瑪-胺基丁酸B型受體-胞外信號調節激酶途徑在藍斑核神經元之角色探討 | zh_TW |
dc.title | Role of GABAB receptor - extracellular signal - regulated kinase pathway in Locus Coeruleus neurons | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 楊琇雯(Hsiu-Wen Yang),陳志成(Chih-Cheng Chen),陳瑞芬(Ruei-Feng Chen) | |
dc.subject.keyword | 藍斑核,伽瑪-胺基丁酸B型受體,胞外信號調節激?1/2,受體運輸, | zh_TW |
dc.subject.keyword | Locus Coeruleus,GABAB receptor,extracellular signal-regulated kinase 1/2,receptor trafficking, | en |
dc.relation.page | 79 | |
dc.identifier.doi | 10.6342/NTU201601733 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-08-04 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生命科學系 | zh_TW |
顯示於系所單位: | 生命科學系 |
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