Olivier H. Thibault, Ph.D.
Associate Professor
Bowman Gray School of Medicine, Wake Forest University, 1993.
Office: MS-320 Chandler Medical Center (0298)
Lab: MS-231; (859) 323-6259
Tel: (859) 323-4863
Calcium electrophysiology/imaging and brain aging correlates
Current Projects
Research centers around the study of Voltage-Gated and Ligand-Gated Ca2+ Channels in the hippocampus of aging animals during synaptic activation of CA1 pyramidal neurons. These two types of plasmamembrane channels are responsible for raising intracellular Ca2+ levels (or at least participating in the early events of Ca2+signaling), and have also been implicated in mediating / triggering appropriate downstream cognitive functions. Overwhelming evidence indicates that elevated postsynaptic intracellular Ca2+ levels can modulate neuronal communication and throughput. Electrophysiological patch clamp as well as sharp electrode techniques, combined with ratiometric and non-ratiometric Ca2+ imaging, are the primary tools used to detect aging-dependent changes in Ca2+. Routine assessments of the Ca2+ status in a single neuron combined with concomitant recording of electrophysiological parameters in that same neuron are used to determine the physiological and pathophysiological roles of Ca2+ influx and release, and to determine if these Ca2+ changes impart the weaker synaptic phenotype seen in brain aging and possibly Alzheimer's disease.
Selected Publications
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Pancani T., Phelps J.T., Searcy J.L., Kilgore M.W., Porter N.M., and Thibault O.(2009)
Distinct modulation of voltage-gated and ligand-gated Ca2+ currents by PPAR-γ agonists in cultured hippocampal neurons. J. Neurochem., 109:1800-1811.
Kadish I. , Thibault O., Blalock E.M., Chen, K.-C., Gant J.C., Porter N.M., and Landfield P.W. (2009)
Onset of hippocampal and cognitive aging: Lifespan expression analyses identify associated changes in metabolism and cholesterol trafficking.
J. Neurosci., 29:1805-1816.
Gant J.C., Thibault O., Blalock E.M., Yang J., Bachstetter A., Kotick J., Schauwecker P.E., Hauser K.F., Smith G.M., Mervis R., Li Y., and Barnes G.N. (2009)
Decreased number of interneurons and increased seizures in neuropilin 2 deficient mice: implications for autism and epilepsy.
Epilepsia. 2009 Apr;50(4):629-45. Epub 2008 Jul 24.
Norris C.M., Blalock E.M., Chen K.C., Porter N.M., Thibault O., Kraner S.D., and Landfield P.W. (2008)
Hippocampal 'zipper' slice studies reveal a necessary role for calcineurin in the increased activity of L-type Ca(2+) channels with aging.
Neurobiol Aging. 2008 May 7. [Epub ahead of print]
Gant, J.C., Thibault,O., Blalock, E.M., Yang, J., Bachstetter, A., Kotick J., Schauwecker P.E., Hauser, K.F, Smith, G.M., Mervis, R., Li Y.F., and Barnes, G.N. (2008)
Decreased number of interneurons, and increased seizures in neuropilin 2 deficient mice: implications for autism and epilepsy. Epilepsia 2008. Epub doi: 10.1111/j.1528-1167.2008.01725.x
Gant J.C., and Thibault O. (2008)
Action potential generation in aged rat hippocampal neurons: regulation by selective forms of hyperpolarization. Neurobiology of Aging 2008. Epub doi:10.1016/j.neurobiolaging.2008.02.006
Norris C.M., Blalock E.M., Chen K.-C., Porter N.M., Thibault O., Kraner S.D., and Landfield, P.W. Hippocampal “zipper” slice studies reveal a necessary role for calcineurin in the increased activity of L-type Ca2+ channels with aging. Neurobiology of Aging 2008. Epub doi:10.1016/j.neurobiolaging.2008.03.026
Thibault,O., Gant J.C. and Landfield P.W. (2007)
Expansion of the Calcium hypothesis of brain aging and Alzheimer’s disease: minding the store. Aging Cell 6: 307-317.
Brewer L.D., Thibault O., Rogers J.T., Staton J., Thibault V., Kraner S., Landfield P.W., Porter N.M. (2007)
Increased vulnerability of hippocampal neurons with age in culture: temporal association with increases in NMDA receptor current, NR2A subunit expression and recruitment of L-type Calcium channels.
Brain Research 1151:20-31.
Rowe* WB, Blalock* EM, Chen KC, Kadish I, Wang D, Barrett JE, Thibault O, Porter NM, Rose GM, Landfield PW (2007)
Hippocampal Expression Analyses Reveal Selective Association of Immediate-Early, Neuroenergetic, and Myelinogenic Pathways with Cognitive Impairment in Aged Rats.
J Neurosci 27: 3098-3110
Brewer L.D., Porter N.M., Kerr, S.D., Landfield P.W. and Thibault O. (2006)
Chronic 1α,25-(OH)2vitamin D3 treatment reduces Ca2+-mediated hippocampal biomarkers of aging.
Cell Calcium 40: 277-286.
Norris C.M., Blalock E.M., Thibault O., Porter N.M. and Landfield P.W. (2006)
Electrophysiological mechanisms of delayed excitotoxicity: positive feed back loop between NMDA receptor current and depolarization-mediated glutamate release.
J. Neurophysiol. 96(5): 2488 – 2500.
Kelly K., Nadon N., Morrison J., Thibault O., Barnes C.A., and Blalock E.M. (2006)
The neurobiology of aging. Epilepsy Res. 68S: S5-S20.
Gant J.C., Sama M.A., Landfield P.W., Thibault O. (2006)
Early and simultaneous emergence of multiple hippocampal biomarkers of aging is mediated by Ca2+-release. J. Neurosci. 26: 3482-3490.
Attucci S, Clodfelter GV, Thibault O, Staton J, Moroni F, Landfield PW, Porter NM.(2002)
Group I metabotropic glutamate receptor inhibition selectively blocks a prolonged Ca(2+) elevation associated with age-dependent excitotoxicity.
Neuroscience 112:183-194.
Thibault O, Hadley R, Landfield PW. (2001)
Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity.
J Neurosci 21:9744-9756.
Chen K-C, Blalock EM, Thibault O, Kaminker P and Landfield PW. (2000)
Expression of a1D subunit mRNA is correlated with L-type Ca2+ channel activity in single neurons of hippocampal "zipper" slices.
PNAS 97(8):4357-4362.
Thibault O, Porter NM, Chen K-C, Kaminker PG, Blalock EM, Clodfelter GV, Brewer L and Landfield PW. (1998)
Calcium dysregulation in neuronal aging and Alzheimer's disease: history and new directions.
Cell Calcium, 24 (5/6): 417-433.
Porter NM, Thibault O, Thibault V, Chen K-C and Landfield PW (1997).
Calcium channel density and hippocampal cell death with age in long-term culture.
J Neurosci 17:5629-5639.
Thibault O and Landfield PW. (1996)
Increase in single L-type calcium channels in hippocampal neurons during aging.
Science 272:1017-1020.
Campbell LW, Hao S-Y, Thibault O, Blalock EM and Landfield PW. (1996)
Aging changes in voltage-gated calcium currents in hippocampal CA1 neurons.
J Neurosci 16: 6286-6295.
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