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Senior Investigator

Jerrel Louis Yakel, Ph.D.


P.O. Box 12233
Research Triangle Park NC 27709-
Office: (919) 541-1407

Fax: (919) 316-4653
yakel@niehs.nih.gov

Dr. Yakel received his B.S. from Oregon State University, and his Ph.D. from the University of California, Los Angeles, where he studied ligand-gated ion channels and serotonin receptors in cultured hippocampal neurons and cell lines with Meyer Jackson. During a postdoctoral fellowship with Hersch Gerschenfeld at the Ecole Normale Superieure (Paris, France), he investigated the regulation of voltage-gated calcium channels by G protein-coupled receptors. During a second postdoctoral stage at the Vollum Institute with Alan North and Tom Soderling, he studied the function of regulation of ligand-gated ion channels. Dr. Yakel joined NIEHS as an investigator in 1993, and is currently a Senior Investigator in the Laboratory of Neurobiology. His laboratory explores the function and regulation of ligand-gated ion channels, in particular the neuronal nicot



The Ion Channel Physiology Group studies the structure, function and regulation of the Cys-loop ligand-gated ion channel superfamily, with a particular focus on the nicotinic acetylcholine receptor channels and their role in neurological disorders.

The neuronal nicotinic acetylcholine receptor channels (nAChRs) are expressed throughout the central and peripheral nervous system and are involved in a variety of normal brain functions including cognitive tasks, neuronal development, and mediating the rewarding effects of nicotine. The nAChRs are expressed both pre- and postsynaptically where they influence neuronal signaling, and are therefore a significant therapeutic target for many neurodegenerative, neurological, and psychiatric disorders such as Alzheimer's disease, Parkinson's disease, epilepsy and schizophrenia. A growing body of evidence indicates that many neurodegenerative diseases and disorders including Alzheimer's disease may be linked to environmental exposures. Therefore it is critical that the relative roles of environmental and endogenous neurochemicals in the susceptibility and progression of neurodegenerative diseases and disorders be investigated. To achieve that goal and to develop therapeutic agents that may help in the treatment of these diseases, it will be essential to understand the basic mechanisms of neuronal signaling.

Major areas of research include nicotinic receptor regulation of and by calcium-dependent signal transduction cascades, the role of nicotinic receptors in excitability of neuronal circuits in the hippocampus and substantia nigra, and structure/function aspects of peptide interaction and inhibition of nicotinic receptor. Current projects include: Function and expression of nicotinic receptors in substantia nigra, and potential role in Parkinson's disease, structural determinates for apolipoproteinE-derived peptide interaction with the α7 nicotinic acetylcholine receptor, dendritic calcium signaling due to activation of α7-containing nicotinic acetylcholine receptors in rat hippocampal neurons, and voltage-sensitive dye recording to study hippocampal excitability and circuits regulated by nicotinic receptor activation.

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  • Qing Cheng, Ph.D.
    Research Fellow

  • Joanne Damborsky, Ph.D.
    IRTA Fellow

  • Zhenglin Gu
    Research Fellow

  • Juhee Haam, Ph.D.
    Visiting Fellow

  • Patricia Lamb, B.S.
    Senior Research Assistant
    (919) 541-2662

  • Simone Otto, Ph.D.
    IRTA Fellow

  • 1) Cheng, Q. & Yakel, J.L (2014)
  • Presynaptic apha7 nicotinic acetylcholine receptors enhance hippocampal mossy fiber glutamatergic transmission via PKA activation
  • Journal of Neuroscience, 34, 124-133
  • 2) Cheng, Q. & Yakel, J.L (2014)
  • Presynaptic apha7 nicotinic acetylcholine receptors enhance hippocampal mossy fiber glutamatergic transmission via PKA activation
  • Journal of Neuroscience, 34, 124-133
  • 3) Pandya AA, Yakel JL (2013)
  • Activation of the alpha7 nicotinic ACh receptor induces anxiogenic effects in rats which is blocked by a 5-HT(1a) receptor antagonist
  • Neuropharmacology
  • 4) Pandya AA, Yakel JL. (2013)
  • Effects of neuronal nicotinic acetylcholine receptor allosteric modulators in animal behavior studies
  • Biochem Pharmacol.
  • 5) Yakel JL (2013)
  • Cholinergic receptors: functional role of nicotinic ACh receptors in brain circuits and disease
  • Pflugers Archives
  • 6) Colon-Saez, J. & Yakel, J.L (2013)
  • A mutation in the extracellular domain of the alpha7 nAChR reduces calcium permeability.
  • Pflugers Archives
  • 7) Shen JX and Yakel JL (2012)
  • Functional alpha7 nicotinic ACh receptors on astrocytes in rat hippocampal CA1 slices
  • J Mol Neurosci.
  • 8) Yakel JL (2012)
  • Nicotinic ACh receptors in the hippocampus: role in excitability and plasticity
  • Nicotine Tob Res
  • 9) Gu Z, Lamb PW, & Yakel JL (2012)
  • Cholinergic coordination of presynaptic and postsynaptic activity induces timing-dependent hippocampal synaptic plasticity
  • Journal of Neuroscience
  • 10) Billen B, Spurny R, Brams M, van Elk R, Valera-Kummer S, Yakel JL, Voets T, Bertrand D, Smit AB, & Ulens C (2012)
  • Molecular actions of smoking cessation drugs at alpha4beta2 nicotinic receptors defined in crystal structures of a homologous binding protein
  • Proc Natl Acad Sci U S A.
  • 11) Brams, M., Gay, E.A., Colon Saez, J.,Guskov, A., van Elk, R., van der Schors, R.C., Peigneur, S., Tytgat, J., Strelkov, S.V., Smit, A.B., Yakel, J.L. & Ulens, C (2011)
  • Crystal structures of a cysteine-modified mutant in loop D of acetylcholine binding protein
  • Journal of Biological Chemistry, 286, 4420-4428
  • 12) Gu, Z. & Yakel, J.L (2011)
  • Timing-dependent septal cholinergic induction of dynamic hippocampal synaptic plasticity
  • Neuron, 71, 155-165
  • 13) Colon-Saez, J. & Yakel, J.L (2011)
  • The alpha7 nAChR function in hippocampal neurons is regulated by the lipid composition of the plasma membrane
  • Journal of Physiology, 589, 3163-3174
  • 14) Brams, M., Pandya, A., Kuzmin, D., van Elk, R., Krijnen, L., Yakel, J.L., Tsetlin, V., Smit, A.B., & Ulens, C (2011)
  • A Structural and Mutagenic Blueprint for Molecular Recognition of Strychnine and d-Tubocurarine by Different Cys-Loop Receptors
  • PLoS Biology , 9, e1001034
  • 15) Johnstone, T.B., Gu, Z., Yoshimura, R.F., Villegier, A.S., Hogenkamp, D.J., Whittemore, E.R., Huang, J.C., Tran, M.B., Belluzzi, J.D., Yakel, J.L. & Gee, K.W (2011)
  • Allosteric modulation of related ligand-gated ion channels synergistically induces long term potentiation in the hippocampus and enhances cognition
  • J. Pharm. Exp. Ther, 336, 908-915
  • 16) McCormack, T.J., Melis, C., Colon, J., Gay, E.A., Mike, A., Karoly, R., Lamb, P.W., Molteni, C. & Yakel, J.L. (2010)
  • Rapid Desensitization of the Rat alpha7 nAChR is Facilitated by the Presence of a Proline Residue in the Outer beta-Sheet
  • Journal of Physiology, 588, 4415-4429
  • 17) McCormack, T.J., Melis, C., Colon, J., Gay, E.A., Mike, A., Karoly, R., Lamb, P.W., Molteni, C. & Yakel, J.L. (2010)
  • Rapid Desensitization of the Rat alpha7 nAChR is Facilitated by the Presence of a Proline Residue in the Outer beta-Sheet
  • Journal of Physiology, 588, 4415-4429
  • 18) McCormack, T., Petrovich, R.M., Mercier, K.A., DeRose, E.F., Cuneo, M.J., Williams, J., Johnson, K.L., Lamb, P.W., London, R.E. & Yakel, J.L. (2010)
  • Identification and Functional Characterization of a Novel Acetylcholine-binding Protein from the Marine Annelid Capitella teleta
  • Biochemistry , 49, 2279-2287
  • 19) Seipel, A.T. & and Yakel, J.L. (2010)
  • The frequency-dependence of the nicotine-induced inhibition of dopamine is controlled by the á7 nicotinic receptor
  • J. Neurochemistry, 114, 1659-1666
  • 20) Timofeeva, O.A., Eddins, D., Yakel, J.L., Blackshear, P.J. & Levin ED (2010)
  • Hippocampal infusions of MARCKS peptides impair memory of rats on the radial-arm maze
  • Brain Res. , 1308, 147-152
  • 21) Yakel, J.L. (2010)
  • Gating of nicotinic ACh receptors: latest insights into ligand binding and function
  • J. Physiology , 588, 597-602
  • 22) Eddins, D., Klein, R.C., Yakel, J.L. & Levin, E.D. (2009)
  • Hippocampal infusions of apolipoprotein E peptides induce long-lasting cognitive impairment
  • Brain Res. Bull, 79, 111-115
  • 23) Shen, J.X. & Yakel, J.L. (2009)
  • Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system
  • Acta Pharmacol Sin, 30, 673-680
  • 24) Tu B, Gu Z, Shen JX, Lamb PW, Yakel JL. (2009)
  • Characterization of a nicotine-sensitive neuronal population in rat entorhinal cortex
  • Journal of Neuroscience, 10436-48, 10436-48
  • 25) Shen JX, Tu B, Yakel JL. (2009)
  • Inhibition of alpha7-containing nicotinic ACh receptors by muscarinic M1 ACh receptors in rat hippocampal CA1 interneurones in slices
  • Journal of Physiology, 587, 1033-42
  • 26) Tu B, Gu Z, Shen JX, Lamb PW, Yakel JL. (2009)
  • Characterization of a nicotine-sensitive neuronal population in rat entorhinal cortex
  • Journal of Neuroscience, 10436-48, 10436-48
  • 27) Gay EA, Giniatullin R, Skorinkin A, Yakel JL. (2008)
  • Aromatic residues at position 55 of rat alpha7 nicotinic acetylcholine receptors are critical for maintaining rapid desensitization
  • Journal of Physiology, 586, 1105-15
  • 28) Poisik OV, Shen JX, Jones S, Yakel JL. (2008)
  • Functional alpha7-containing nicotinic acetylcholine receptors localize to cell bodies and proximal dendrites in the rat substantia nigra pars reticulata
  • Journal of Physiology, 586, 1365-78
  • 29) Gay, E.A, Klein, R.C., Melton, M.A., Blackshear, P.J. & Yakel, J.L. (2008)
  • Inhibition of Native and Recombinant Nicotinic Acetylcholine Receptors by the Myristoylated Alanine-Rich C Kinase Substrate Peptide
  • J. Pharm. Exp. Ther. , 327, 884-890
  • 30) Gay EA, Bienstock RJ, Lamb PW, & Yakel JL. (2007)
  • Structural determinates for apolipoprotein E-derived peptide interaction with the alpha7 nicotinic acetylcholine receptor
  • Mol. Pharmacology, 72, 838-849
  • 31) Gay EA, Bienstock RJ, Lamb PW, Yakel JL. (2007)
  • Structural determinates for apolipoprotein E-derived peptide interaction with the alpha7 nicotinic acetylcholine receptor
  • Molecular Pharmacology, 72, 838-49
  • 32) Fayuk D & Yakel JL. (2007)
  • Dendritic Ca2+ signalling due to activation of alpha 7-containing nicotinic acetylcholine receptors in rat hippocampal neurons
  • J. Physiology, 582, 597-611
  • 33) Gay, E.A., Klein, R.C. & Yakel, J.L. (2006)
  • Apolipoprotein E-derived peptides block alpha7 neuronal nicotinic acetylcholine receptors expressed in xenopus oocytes
  • J. Pharm. Exp. Ther., 316, 835-842
  • 34) Klein, R.C. & Yakel, J.L. (2006)
  • Functional somato-dendritic alpha7-containing nicotinic acetylcholine receptors in the rat basolateral amygdala complex
  • J. Physiology, 576, 865-872
  • 35) Klein, R.C. & Yakel, J.L. (2005)
  • Paired-pulse potentiation of alpha7-containing nAChRs in rat hippocampal CA1 stratum radiatum interneurones
  • J. Physiology, 568, 881-889
  • 36) Fayuk, D. & Yakel, J.L. (2005)
  • Ca2+ permeability of nicotinic acetylcholine receptors in rat hippocampal CA1 interneurons
  • J. Physiology, 566, 759-768
  • 37) Giniatullin, R., Nistri, A. & Yakel, J.L. (2005)
  • Desensitization of Nicotinic ACh Receptors: Shaping Cholinergic Signaling
  • Trends in Neurosciences, 28, 371-378
  • 38) Lamb, P.W., Melton, M.A. & Yakel, J.L. (2005)
  • Inhibition of neuronal nicotinic acetylcholine receptor channels expressed in Xenopus oocytes by beta-amyloid1-42 peptide
  • J. Mol. Neuroscience, 27, 13-22
  • 39) Yakel, J.L. & Shao, Z. (2004)
  • Functional and Molecular Characterization of Neuronal Nicotinic ACh Receptors in Rat Hippocampal Interneurons
  • Progress in Brain Research, 145, 95-107
  • 40) Khiroug, S., Khiroug, L., & Yakel, J.L. (2004)
  • Rat nicotinic ACh receptor alpha2beta2 channels:
  • Neuroscience, 124, 817-822
  • 41) Klein, R.C. & Yakel, J.L. (2004)
  • Inhibition of nicotinic acetylcholine receptors by Apolipoprotein E-derived peptides in rat hippocampal slices
  • Neuroscience (Rapid Report) , 127, 563-567
  • 42) Fayuk, D. & Yakel, J.L. (2004)
  • Regulation of nicotinic acetylcholine receptor channel function by acetylcholinesterase inhibitors in rat hippocampal CA1 interneurons
  • Mol. Pharmacology, 66, 658-666
  • 43) Khiroug, L., Giniatullin, R., Klein, R.C., Fayuk, D. & Yakel, J.L (2003)
  • Functional mapping and Ca2+ regulation of nicotinic acetylcholine receptor channels in rat hippocampal CA1 neurons
  • J. Neuroscience, 23, 9024-9031
  • 44) van Hooft JA, and Yakel JL (2003)
  • 5-HT(3) receptors in the CNS: 3B or not 3B?
  • Trends Pharmacol Sci., 24, 157-160
  • 45) Jones S, Yakel JL. (2003)
  • Casein kinase II (protein kinase CK2) regulates serotonin 5-HT(3) receptor channel function in NG108-15 cells.
  • Neuroscience, 119, 629-634
  • 46) Sudweeks S.N., Hooft J.A., and Yakel J.L. (2002)
  • Serotonin 5-HT(3) receptors in rat CA1 hippocampal interneurons: functional and molecular characterization
  • Journal of Physiology, 544, 715-726
  • 47) Khiroug, S.S., Harkness, P.C., Lamb, P.W., Sudweeks, S.N., Khiroug, L., Millar, N.S., & Yakel, J.L. (2002)
  • Rat nicotinic ACh receptor alpha7 and beta2 subunits co-assemble to form functional heteromeric nicotinic receptor channels
  • J. Physiology, 540, 425-434
  • 48) Pettit, D.L., Shao, Z. and Yakel, J.L. (2001)
  • Beta-Amyloid 1-42 peptide directly modulates nicotinic receptors in the rat hippocampal slice
  • J. Neuroscience, 21, RC120
  • 49) Shao, Z. and Yakel, J.L. (2000)
  • Single channel properties of neuronal nicotinic ACh receptors in stratum radiatum interneurons of rat hippocampal slices
  • J. Physiology, 527, 507-513
  • 50) Sudweeks, S, and Yakel, J.L. (2000)
  • Functional and molecular characterization of neuronal nicotinic ACh receptors in rat CA1 hippocampal neurones
  • J. Physiology, 527, 515-528
  • 51) Jones, S., Sudweeks, S. & Yakel, J.L. (1999)
  • Nicotinic receptors in the brain: correlating physiology with function
  • Trends in Neurosciences , 22, 555-561
  • 52) Kriegler, S., Sudweeks, S, & Yakel, J.L. (1999)
  • MTSEA potentiates 5-HT3 receptors containing the nicotinic alpha4 subunit
  • Neuropharmacology, 38, 1913-1915
  • 53) Kriegler, S., Sudweeks, S, and Yakel, J.L. (1999)
  • The nicotinic alpha4 receptor subunit contributes to the lining of the ion channel pore when expressed with the 5-HT3 receptor subunit
  • J. Biol. Chemistry, 274, 3934-3936
  • 54) Jones, S., & Yakel, J.L. (1998)
  • Ca2+ influx through voltage-gated Ca2+ channels regulates 5-HT3 receptor channel desensitization in rat glioma X mouse neuroblastoma hybrid NG108-15 cells
  • J. Physiology , 510, 361-370
  • 55) Van Hooft, J.A., Spier, A.D., Yakel, J.L., Lummis, S.C.R., and Vijverberg, H.P.M. (1998)
  • Promiscuous coassembly of serotonin 5-HT3 and nicotinic alpha4 receptor subunits into Ca2+ permeable ion channels
  • Proc. Natl. Acad. Sci, 95, 11456-11461
  • 56) Zhu, Y., & Yakel, J.L. (1997)
  • Calcineurin modulates G protein-mediated inhibition of N-type
  • J. Neurophysiol, 78, 1161-1165
  • 58) Gilon, P., Yakel, J., Gromada, J., Zhu, Y., Henquin, J-C., & Rorsman, P. (1997)
  • G-protein-dependent inhibition of L-type Ca2+ currents by acetylcholine in mouse pancreatic B-cells
  • J. Physiology, 499, 65-76
  • 59) Zhu, Y., & Yakel, J.L. (1997)
  • Modulation of Ca2+ currents by various G protein-coupled
  • J. Neurophysiol, 78, 780-789
  • 60) Jones, S., & Yakel, J.L. (1997)
  • Functional nicotinic ACh receptors on interneurones in the rat
  • J. Physiology , 504, 603-610
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