Zhen Yan, Ph.D.
    

                         Professor
   

Department of Physiology and Biophysics

School of Medicine & Biomedical Sciences

State University of New York at Buffalo

 


Research Interests:  

Mechanisms for the Regulation of Ligand-gated Ion Channels and Synaptic Transmission

     Information processing in the central nervous system (CNS) is achieved by the interplay between chemical and electrical signals. Neurotransmitters (e.g. serotonin, dopamine, acetylcholine) and hormones (e.g. corticosteroid) influence CNS functions by regulating ion channels, which can produce short-term changes in membrane excitability and long-term changes in synaptic plasticity. Dysfunctions of these neuromodulators in specific brain regions have been implicated in the pathogenesis of various mental disorders, including Schizophrenia, depression and Alzheimer’s disease. One of our major goals is to understand how these neuromodulators regulate ligand-gated ion channels and synaptic transmission in prefrontal cortex, a key region controlling cognition and emotion.

     Neuromodulators exert their actions through G protein-coupled receptors or nuclear hormone receptors. These receptors link to various intracellular signaling cascades, which potentially influence different ion channels in a specific and coordinated manner.  We use a combination of multiple approaches to reveal signal transduction pathways mediated by neuromodulators.  Specifically,

Our studies will provide knowledge on the molecular and cellular mechanisms underlying the regulation of synaptic transmission by neuromodulators, which is important for mental health and diseases.

 

Keywords:

prefrontal cortex; G protein-coupled receptors; stress hormones; NMDA/AMPA receptor channels; GABAA receptor channels; protein kinases and phosphatases; cytoskeleton; trafficking; scaffolding proteins; disease susceptibility genes.

 

Contact Information:

Email:                            zhenyan@buffalo.edu
Tel:                                (716) 829-3058 (office), (716) 829-3592 (lab)
Fax:                               (716) 829-2699
Lab location:                  Biomedical Research Building (BRB) Rm. 546-550, Rm. 545

Office location:              BRB Rm. 551 

Mailing address:            124 Sherman Hall, Buffalo, NY 14214

 

Recent Selective Peer-Reviewed Publications:  

2014

·        Cheng J, Xiong Z, Duffney LJ, Wei J, Liu AY, Liu S, Chen GJ, Yan Z (2014) Methylphenidate exerts dose-dependent effects on glutamate receptors and behaviors. Biol. Psychiatry (in press). [PDF file]

·       Zhong P and Yan Z (2014) Distinct physiological effects of dopamine D4 receptors on prefrontal cortical pyramidal neurons and fast-spiking interneurons. Cerebral Cortex (in press). [PDF file]

·       Yuen EY, Qin L, Wei J, Liu W, Liu A and Yan Z (2014) Synergistic regulation of glutamatergic transmission by serotonin and norepinephrine reuptake inhibitors in prefrontal cortical neurons. J. Biol. Chem. 289:25177-85. [PDF file]

·       Gu Z, Cheng J, Zhong P, Qin L, Liu W, Yan Z (2014) Ab selectively impairs mGluR7 modulation of NMDA signaling in basal forebrain cholinergic neurons: implication in Alzheimer’s disease. J. Neurosci. (in press).

·       Smith KR, Davenport EC, Wei J, Li X, Pathania M, Vaccaro V, Yan Z, Kittler JT (2014) GIT1 and bPIX link Rac1 signalling to GABAA receptor cluster stability and inhibitory synapse strength. Cell Reports (in press).

·       Plattner F, Hernandez A, Kistler TM, Pozo K, Zhong P, Yuen EY, Tan C, Hawasli AH, Cooke SF, Nishi A, Guo A, Weiderhold T, Yan Z, Bibb JA (2014) Memory enhancement by targeting Cdk5 regulation of NR2B. Neuron 81:1070-83. [PDF file]

·       Hayashi-Takagi A, Araki Y, Nakamura M, Vollrath B, Duron SG, Yan Z, Kasai H, Huganir RL, Campbell DA, Sawa A (2014) PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence. Proc. Natl. Acad. Sci. USA 111:6461-6. [PDF file]

·       Wei J, Graziane NM, Wang H, Zhong P, Wang Q, Liu W, Hayashi-Takagi A, Korth C, Sawa A, Brandon NJ, Yan Z (2014) Regulation of NMDA receptors by Disrupted-in-Schizophrenia-1 (DISC1). Biol. Psychiatry 75:414-24. [PDF file]

·       Deng Y, Xiong Z, Chen P, Wei J, Chen SD, Yan Z (2014) b-Amyloid Impairs the regulation of NMDA receptors by Glycogen Synthase Kinase 3. Neurobiol. Aging  35:449-59. [PDF file]

·       Wei J, Yuen EY, Liu W, Li X, Zhong P, Karatsoreos IN, McEwen BS, Yan Z (2014) Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition. Molecular Psychiatry 19:588-98. [PDF file] *Recommended as being of special significance in its field by Faculty of 1000 and selected for F1000Prime; reported in Los Angeles Times, Chicago Tribune, England’s Daily Mail, Huffington Post, WPEC-TV CBS 12 News, etc.

2013

·       Duffney LJ, Wei J, Cheng J, Liu W, Smith KR, Kittler JT, Yan Z (2013) Shank3 deficiency induces NMDA receptor hypofunction via an actin-dependent mechanism. J. Neurosci. 33:15767-78. [PDF file]

·       Vithlani M, Hines RM, Zhong P, Terunuma M, Hines DJ, Revilla-Sanchez R, Jurd R, Haydon P, Rios M,  Brandon N, Yan Z, Moss SJ (2013) Effects of BNDF on neurogenesis and depression depend upon phosphorylation of the GABAAR g2 subunit. J. Neurosci.  33:15567-77. [PDF file] 

·       Cheng J, Liu W, Duffney LJ, Yan Z (2013) SNARE proteins are essential in the potentiation of NMDAR currents by group II metabotropic glutamate receptors. J. Physiol. 591:3935-47. [PDF file]

·       Yuen EY, Zhong P, Li X, Wei J, Yan Z (2013) Restoration of glutamatergic transmission by dopamine D4 receptors in stressed animals. J. Biol. Chem. 288:26112-20. [PDF file]

·       Chen GJ, Xiong  Z, Yan Z (2013) Ab impairs nicotinic regulation of inhibitory synaptic transmission and interneuron excitability in prefrontal cortex. Molecular Neurodegeneration 8:3. [PDF file]

2012

·        Yuen EY, Wei J, Liu W, Zhong P, Li X, Yan Z (2012) Repeated stress causes cognitive impairment by suppressing glutamate receptor expression and function in prefrontal cortex. Neuron 73:962-77. [PDF file] *Featured by the Cell Press (March 2012).

·        Lee JB, Wei J, Liu W, Cheng J, Feng J, Yan Z (2012) Histone Deacetylase 6 gates the synaptic action of acute stress in prefrontal cortex. J. Physiology 90:1535-46. [PDF file]

·        Yuen EY, Wei J, Zhong P, Yan Z (2012) Disrupted GABAAR trafficking and synaptic inhibition in a mouse model of Huntington’s disease. Neurobiology of Disease 46:497-502. [PDF file]

·        Jiang H, Ren Y, Yuen EY, Zhong P, Ghaedi M, Hu Z, Azabdaftari G,  Nakaso K, Yan Z, Feng J (2012) Parkin controls dopamine utilization in human midbrain dopaminergic neurons. Nature Communications 3:668. [PDF file]

·        Gu Z, Liu W, Wei J, Yan Z (2012) Regulation of NMDA receptors by metabotropic glutamate receptor 7. J. Biol. Chem. 287:10265-75. (selected as "Papers of the Week") [PDF file]

·        Yuen EY, Li X, Wei J, Horiguchi M, Meltzer HY, Yan Z (2012) The novel antipsychotic drug lurasidone enhances NMDA receptor-mediated synaptic responses. Mol. Pharm. 81:113-9. [PDF file]

2011

·       Popoli M, Yan Z, McEwen BS, Sanacora G (2011) The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nature Review Neuroscience 13:22-37. [PDF file]

·       Yuen EY, Liu W, Karatsoreos IN, Ren Y, Feng J, McEwen BS, Yan Z (2011) Mechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory. Mol. Psychiatry 16:156-70. [PDF file] [supporting information] (cover article)

·       Mandal M, Wei J, Zhong P, Chen J, Duffney LJ, Liu W, Yuen EY, Twelvetrees AE, Li S, Li XJ, Kittler JT, Yan Z (2011) Impaired AMPA receptor trafficking and function by mutant huntingtin. J. Biol. Chem. 286:33719-28. [PDF file]

·        Zhong P, Yan Z (2011) Differential regulation of the excitability of prefrontal cortical fast-spiking interneurons and pyramidal neurons by serotonin and fluoxetine. PLoS One  6(2):e16970. [PDF file]

·        Yuen EY, Yan Z (2011) Cellular mechanisms for the dopamine D4 receptor-induced homeostatic regulation of AMPA receptors. J. Biol. Chem. 286:24957-65. [PDF file]

·        Wang Q, Charych EI, Pulito VL, Lee JB, Graziane NM, Crozier RA, Revilla-Sanchez R, Kelly MP, Dunlop AJ, Murdoch H, Taylor N, Xie Y, Pausch M, Hayashi-Takagi A, Ishizuka K, Seshadri S, Bates B, Kariya K, Sawa A, Weinberg RJ, Moss SJ, Houslay MD, Yan Z, Brandon NJ (2011) The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function. Mol Psychiatry 16:1006-23. [PDF file]

·        Wang D, Yuen EY, Zhou Y, Yan Z, Xiang YK (2011) Amyloid {beta} peptide1-42 induces internalization and degradation of {beta}2 adrenergic receptor in prefrontal cortical neurons. J Biol Chem. 286:31852-63. [PDF file]

·        Liu W, Dou F, Feng J, Yan Z (2011) RACK1 is involved in b-amyloid impairment of muscarinic regulation of GABAergic transmission. Neurobiol. Aging 32:1818-26. [PDF file]

2010

·       Yuen EY, Zhong P, Yan Z (2010) Homeostatic regulation of glutamatergic transmission by dopamine D4 receptors. Proc. Natl. Acad. Sci. USA107:22308-13. [PDF file] [supporting information] 

·       Liu W, Yuen EY, Yan Z (2010) The stress hormone corticosterone increases synaptic AMPA receptors via SGK regulation of the GDI-Rab4 complex. J. Biol. Chem. 285:6101-8. [PDF file]

·       Wei J, Liu W, Yan Z (2010) Regulation of AMPA receptor trafficking and function by glycogen synthase kinase 3. J. Biol. Chem. 285:26369-76. [PDF file]

·       Yuen EY, Liu W, Kafri T, van Praag H, Yan Z (2010) Regulation of AMPA receptor channels and synaptic plasticity by cofilin phosphatase Slingshot in cortical neurons. J. Physiol. 588:2361-71. [PDF file]  (cover article)

·       Twelvetrees AE, Yuen EY, Arancibia-Carcamo IL, Rostaing P, Lumb MJ, Humbert S, Triller A, Saudou F, Yan Z, Kittler JT (2010) Delivery of GABAARs to synapses is mediated by HAP1-KIF5 and disrupted by mutant huntingtin. Neuron 65:53-65. [PDF file]

·       Hayashi-Takagi A, Takaki M, Graziane NM, Seshadri S, Murdoch H, Dunlop AJ, Makino Y, Seshadri AJ, Ishizuka K, Srivastava DP, Xie Z, Baraban JM, Houslay MD, Tomoda T, Brandon NJ, Kamiya A, Yan Z, Penzes P, Sawa A (2010) Disrupted-in-Schizophrenia-1 (DISC1) regulates spines of the glutamate synapse via Rac1. Nat. Neurosci. 13:327-32. [PDF file]

·       Joiner MA, Lisé MF, Yuen EY, Kam A, Hall DD, Malik ZA, Qian H, Chen Y, Ulrich JD, Burette AC, Weinberg RJ, Law PY, El-Husseini A, Yan Z, Hell JW (2010) Assembly of a b2-adrenergic receptor- GluR1 signaling complex for localized cAMP signaling. EMBO J 29:482-95. [PDF file]

2009

·       Yuen EY, Liu W, Karatsoreos IN, Feng J, McEwen BS, Yan Z (2009) Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory. Proc. Natl. Acad. Sci. USA 106:14075-9. [PDF file]

·       Mandal M and Yan Z (2009) PIP2 regulation of NMDA receptor channels in cortical neurons. Mol. Pharm. 76:1349-59. [PDF file]

·       Arancibia-Cárcamo IL, Yuen EY, Muir J, Lumb MJ, Michels G, Smart TG, Yan Z, Kittler JT, Moss SJ (2009) Ubiquitin-dependent targeting of GABAARs for lysosomal degradation regulates the efficacy of neuronal inhibition. Proc. Natl. Acad. Sci. USA 106:17552-7. [PDF file]

·       Saliba RS, Gu Z, Yan Z, Moss SJ (2009) Blocking L-type voltage gated Ca2+ channels with dihydropyridines reduces gamma-aminobutyric acid type A receptor expression and synaptic inhibition. J Biol Chem. 284:32544-50.

·        Huang YH, Lin Y, Mu P, Marie H, Liu W, Yan Z, Sorg BA, Schluter O, Zukin SR, Dong Y (2009) Exposure to cocaine generates nascent synapses in the nucleus accumbens. Neuron. 63:40-7. [PDF file]

·       Yuen EY, Yan Z (2009) Dopamine D4 receptors regulate AMPAR trafficking and glutamatergic transmission in GABAergic interneurons of prefrontal cortex. J. Neurosci. 29:550-62. [PDF file]

·        Gu Z, Liu W, Yan Z (2009) b-amyloid Impairs AMPA receptor trafficking and function by reducing CaMKII synaptic distribution. J Biol Chem. 284:10639-49. [PDF file]

·        Graziane NM, Yuen EY, Yan Z (2009) Dopamine D4 receptors regulate GABAA receptor trafficking via an actin/cofilin/myosin-dependent mechanism. J Biol Chem. 284:8329-36. [PDF file]

2008

·       Yuen EY, Jiang Q, Chen P, Feng J, Yan Z (2008) Activation of 5-HT2A/C receptors counteracts 5-HT1A regulation of NMDAR channels in pyramidal neurons of prefrontal cortex. J. Biol. Chem. 283:17194-204. [PDF file]

·        Zhong P, Liu W, Gu Z, Yan Z (2008) Serotonin facilitates LTD induction in prefrontal cortex via p38 MAPK/Rab5-mediated enhancement of AMPA receptor internalization. J. Physiol. 586:4465-79. [PDF file]

·        Yuen EY, Ren Y, Yan Z (2008) PSD-95 and calcineurin control the sensitivity of NMDA receptors to calpain cleavage in cortical neurons. Mol. Pharmacol. 74:360-370.[PDF file]

·       Zhong P, Yuen EY, Yan Z (2008) Modulation of neuronal excitability by serotonin-NMDA interactions in prefrontal cortex. Mol. and Cell. Neurosci. 38:290-9. [PDF file]

·       Kittler JT, Chen G, Kukhtina V, Vahedi-Faridi A, Gu Z, Tretter V, Smith KR, McAinsh K, Arancibia-Carcamo IL, Saenger W, Haucke V, Yan Z, Moss SJ (2008) Regulation of synaptic inhibition by phospho-dependent binding of the AP2 complex to a YECL motif in the GABAA receptor g2 subunit. Proc Natl Acad Sci. USA 105:3616-21. [PDF file]

·       Chen G, Chen P, Tan H, Ma D, Dou F, Feng J, Yan Z (2008) Regulation of the NMDA receptor-mediated synaptic response by acetylcholinesterase inhibitors and its impairment in an animal model of Alzheimer’s disease. Neurobiol. Aging 29:1795-804. [PDF file]

 

 

Publication List        Lab Members         Biographical Information        News Release

 

 

Last updated: 8/2014