Zhen Yan, Ph.D.
    

                         Professor
   

 

Research Interests:

Molecular and Cellular Mechanisms for the Regulation of Ion Channels and Synaptic Transmission in CNS Neurons
     Information processing in the central nervous system (CNS) is achieved by the interplay between chemical and electrical signals. Neuromodulators, such as, serotonin, dopamine and acetylcholine, influence CNS functions by regulating the activity of 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 neuromodulators regulate ion channel functions and synaptic transmission in CNS neurons under normal and pathological conditions.
     Most neuromodulators exert their actions through G protein-coupled receptors. These receptors link to various intracellular signaling cascades, which potentially influence different ion channels in a specific and coordinated manner. A heterogeneous array of receptors, second messengers and ion channels is co-expressed in all CNS neurons. To reveal signal transduction pathways mediated by neuromodulators, we use a combination of multiple approaches. Specifically, electrophysiological techniques, such as whole-cell patch-clamp recordings in dissociated CNS neurons and brain slices, are used to characterize the effect of receptor activation on ion channel function and synaptic transmission. Biochemical and pharmacological approaches are used to identify the signaling molecules linking receptors and channels. Molecular and immunocytochemical techniques are used to detect the expression, localization and trafficking of receptors, ion channels and signaling components in neurons. Moreover, animal models for neurological disorders are used to examine how the neuromodulator actions are altered in these pathological conditions. Our studies will provide important knowledge on the molecular and cellular mechanisms underlying the regulation of neuronal activity by neuromodulators. Insights gained from this work will be valuable for developing new pharmacological agents in the treatment of brain diseases. 

 

Keywords:

prefrontal cortex; schizopherenia; depression and anxiety; stress; Alzheimer's disease; G protein-coupled receptors; serotonin; dopamine; acetylcholine; ligand-gated ion channels; glutamate; GABA; synaptic transmission; regulation; signal transduction; protein kinases and phosphatases; anchoring proteins; cytoskeleton; trafficking; patch-clamp; single-cell RT-PCR; siRNA; antisense oligonucleotides; animal models

 

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, and Rm. 503

Office location:              BRB Rm. 551 

Mailing address:            124 Sherman Hall, Buffalo, NY 14214

 

Recent Publications:  

  • 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 gamma2 subunit. Proc Natl Acad Sci. USA 105:3616-21. [PDF file]

  • Chen P, Gu Z, Liu W, Yan Z (2007) Glycogen synthase kinase 3 regulates NMDA receptor channel trafficking and function in cortical neurons. Mol. Pharm. 72:40-51. [PDF file]

  • Benavides DR, Quinn JJ, Zhong P, Hawasli AH, Kansy JW, DiLeone R, Yan Z, Taylor JR, Bibb JA (2007) Cyclin-dependent protein kinase 5 controls cocaine responses, motivation for reward, and striatal neuron excitability. J. Neurosci. 27:12967-76. [PDF file]

  • Chen G, Chen P, Tan H, Ma D, Dou F, Feng J, Yan Z (2007) Regulation of the NMDA receptor-mediated synaptic response by acetylcholinesterase inhibitors and its impairment in an animal model of Alzheimer’s disease. Neurobiol. Aging (in press). Epub ahead of print. [PDF file]

  • Yuen EY, Liu W, Yan Z (2007) The phosphorylation state of GluR1 subunits determines the susceptibility of AMPA receptors to calpain cleavage. J. Biol. Chem. 282:16434-40. [PDF file]

  • Yuen EY, Gu Z, Yan Z (2007) Calpain regulation of AMPA receptor channels in cortical pyramidal neurons. J Physiol. 580:241-54. [PDF file]

  • Gu Z, Jiang Q, Yan Z (2007) RGS4 modulates serotonin signaling in prefrontal cortex and links to serotonin dysfunction in a rat model of schizophrenia. Mol Pharmacol. 71:1030-9. [PDF file]

  • Kastning K, Kukhtina V, Kittler JT, Chen G, Pechstein A, Enders S, Lee SH, Sheng M, Yan Z, Haucke V (2007) Molecular determinants for the interaction between AMPA receptors and the clathrin adaptor complex AP-2. Proc. Natl. Acad. Sci. USA 104:2991-6. [PDF file]

  • Liu W, Yuen EY, Allen PB, Feng J, Greengard P, Yan Z (2006) Adrenergic modulation of NMDA receptors in prefrontal cortex is differentially regulated by RGS proteins and spinophilin. Proc. Natl. Acad. Sci. USA 103:18338-43. [PDF file]

  • Allen PB, Zachariou V, Svenningsson P, Lepore AC, Centonze D, Costa C, Rossi S, Bender G, Chen G, Feng J, Snyder GL, Bernardi G, Nestler EJ, Yan Z, Calabresi P, Greengard P (2006) Distinct roles for spinophilin and neurabin in dopamine-mediated plasticity. Neuroscience 140:897-911. [PDF file]

  • Jiang Q, Yan Z, Feng J (2006) Neurotrophic factors protect against rotenone toxicity on dopaminergic neurons through a microtubule-dependent mechanism. J. Biol. Chem. 281:29231-400. [PDF file]

  • Jiang Q, Yan Z, Feng J (2006) Activation of group III metabotropic glutamate receptors attenuates rotenone toxicity on dopaminergic neurons through a microtubule-dependent mechanism. J. Neurosci. 26:4318-28. [PDF file]

  • Chen G, Kittler JT, Moss SJ, Yan Z (2006) Dopamine D3 receptors regulate GABA(A) receptor function through a phospho-dependent endocytosis mechanism in nucleus accumbens. J. Neurosci. 26:2511-9. [PDF file]

  • Gu Z,  Jiang Q, Yuen EY, Yan Z (2006) Activation of dopamine D4 receptors induces synaptic translocation of CaMKII in cultured prefrontal cortical neurons. Mol. Pharmacol.  69:813-22. [PDF file]

  • Wang X, Gu Z, Zhong P, Chen G, Feng J, Yan Z (2006) Aberrant regulation of NMDAR functions by dopamine D4 receptors in rats after phencyclidine exposure. Mol. and Cell. Neurosci.  31:15-25. [PDF file]

  • Yuen EY, Jiang Q, Chen P, Gu Z, Feng J, Yan Z (2005) Serotonin 5-HT1A receptors regulate NMDA receptor channels through a microtubule-dependent mechanism. J. Neurosci. 25: 5488-501. [PDF file]

  • Kittler JT, Chen G, Honing S, Bogdanov Y, McAinsh K, Arancibia-Carcamo IL, Jovanovic JN, Pangalos MN, Haucke V, Yan Z and Moss SJ (2005) Phospho-dependent binding of the clathrin AP2 adaptor complex to GABA(A) receptors regulates the efficacy of inhibitory synaptic transmission. Proc. Natl. Acad. Sci. USA 102:14871-6. [PDF file]

  • Gu Z, Jiang Q, Fu AKY, Ip NY, Yan Z (2005) Regulation of NMDA receptors by neuregulin signaling in prefrontal cortex. J. Neurosci. 25: 4974-84. [PDF file]

  • Yuen EY, Jiang Q, Feng J, Yan Z (2005) Microtubule regulation of NMDA receptor channels in neurons. J. Biol. Chem. 280:29420-7. [PDF file]

  • Wu HY*, Yuen EY*, Lu YF, Matsushita M, Matsui H, Yan Z, Tomizawa K (2005) Regulation of NMDA receptors by calpain in cortical neurons. J. Biol. Chem. 280: 21588-93. * co-first author. [PDF file]

  • Chen P, Yan Z (2005) Corticotropin-releasing factor in brain function. In: Handbook of Neurochemistry and Molecular Neurobiology (3rd Edition), (Editor-in-Chief: Abel Lajtha) Kluwer Academic/Plenum Publishers, New York , NY .

  • Tyszkiewicz JP, Yan Z (2005) b-Amyloid peptides impair PKC-dependent functions of metabotropic glutamate receptors in prefrontal cortical neurons. J. Neurophysiol. 93: 3102-11. [PDF file]

 

 

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Last updated: 9/2008