KAREN S. WILCOX
Professor of Pharmacology and Toxicology
Neurobiology of Disease
Electrophysiological mechanisms of action of novel anticonvulsant drugs
The Wilcox laboratory is interested in understanding basic mechanisms underlying epileptogenesis, seizure generation, and therapy-resistance to anticonvulsant drugs. To achieve these goals, we use electrophysiological, genetic, calcium imaging, pharmacological, behavioral, immunoblot, and immunohistochemical techniques in a variety of in vitro preparations and animal models of acquired and genetic forms of epilepsy. Our working hypothesis is that insight into disease-induced changes in neuronal and glial function will provide new avenues for therapeutic interventions in patients at risk for developing epilepsy or those patients who are refractory to current treatment options. To that end, I am also a Co-Investigator in the Anticonvulsant Drug Development (ADD) Program and direct studies determining the neuroprotection potential of proprietary investigational compounds through a contract with NINDS at the National Institutes of Health.
Gee, J.M., Gibbons, M.B., Taheri, M., Palumbos, S., Morris, S.C., Smeal, R.M., Flynn, K.F., Economo, M.N., Cizek, C.G., Capecchi, M.R., Tvrdik, P., Wilcox, K.S., and White, J.A. (2015) Imaging activity in astrocytes and neurons with genetically encoded calcium indicators following in utero electroporation. Front Mol Neurosci, 8:10.
Simonato, M., Brooks-Kayal, A.R., Engel, J. Jr, Galanopoulou, A.S., Jensen, F.E., Moshé, S.L., O'Brien T.J., Pitkanen, A., Wilcox, K.S., and French, J.A. (2014) The challenge and promise of anti-epileptic therapy development in animal models. Lancet Neurol, Sep;13(9):949-960. PMID: 25127174
Gee, J.M., Smith, N.A., Fernandez, F.R., Economo, M.N., Brunert, D. Rothermel, M., Morris, S.C., Talbot, A., Palumbos, S., Ichida, J., Shepherd, J.D., West, P.J., Wachowiak, D.M., Capecchi, M.R., Wilcox, K.S., White, J.A., and Tvrdik, P. (2014) Imaging Activity in Neurons and Glia with a Polr2a-Based and Cre-Dependent GCaMP5G-IRES-tdTomato Reporter Mouse. Neuron, 83(5):1058-1072. PMID: 25155958
West, P.J., Saunders, G.W., Remigio, G.J., Wilcox. K.S., and White, H.S. (2014) Antiseizure drugs differentially modulate θ-burst induced long-term potentiation in C57BL/6 mice. Epilepsia, 55:214-223. PMID: 24447124
Umpierre, A.D., Remigio, G.J., Dahle, E.J., Bradford, K., Alex, A.B., Smith, M.D., West, P.J., White, H.S., and Wilcox, K.S. (2014) Impaired cognitive ability and anxiety-like behavior following acute seizures in the Theiler's virus model of temporal lobe epilepsy. Neurobiol Dis, 64:98-106. PMID: 24412221
Gibbons, M.B., Smeal, R.M., Takahashi, D.K., Vargas, J.R., and Wilcox, K.S. (2013) Contributions of Astrocytes to Epileptogenesis Following Status Epilepticus: Opportunities for Preventive Therapy? Neurochem International, PMID: 23266599
Smeal, R.M., Economo, M.N., Lillis, K.P., Wilcox, K.S., and White, J.A. (2012) Targeted path scanning: an emerging method for recording fast changing network dynamics across large distances. J Bioeng Biomed Sci S5:002. doi: 10.4172/2155-9538.S5-002.
Smeal, R.M., Stewart, K.A., Iacob, E., Fujinami, R.S., White, H.S., and Wilcox, K.S. (2012) The activity within the CA3 excitatory network during Theiler's virus encephalitis is distinct from that observed during chronic epilepsy. Journal of Neurovirology, 18(1):30-44.
Pastuzyn, E.D., Chapman, D.E., Wilcox, K.S., and Keefe, K.A. (2012) Altered learning and Arc-regulated consolidation of learning in striatum by methamphetamine-induced neurotoxicity. Neuropsychopharmacology, 37(4):885-895.
Alex, A.B., Saunders, G.W., Dalpe-Charron, A., Reilly, C.A., and Wilcox, K.S. (2011) CGX-1007 prevents excitotoxic cell death via actions at multiple types of NMDA receptors. Neurotoxicology, 32(4):392-399.
Simeone, T.A., Wilcox, K.S., and Whit, H.S. (2011) Topiramate modulation of beta(1)- and beta(3)-homomeric GABA(A) receptors. Pharmacol Res, 64(1):44-52.
Takahashi, D.K., Vargas, J.R., and Wilcox, K.S. (2010) Increased coupling and altered glutamate transport currents in astrocytes following kainic-acid-induced status epilepticus. Neurobiol of Dis, 40(3):573-585.
Stewart, K.A., Wilcox, K.S., Fujinami, R.S., and White HS. (2010) Development of postinfection epilepsy after Theiler's virus infection of C57BL/6 mice. J Neuropathol Exp Neurol, 69(12):1210-1219.
Libbey, J.E., Kirkman, N.J., Wilcox, K.S., White, H.S., and Fujinami, R.S. (2010) Role for complement in the development of seizures following acute viral infection. J Virol, Jul;84(13):6452-6460.
Otto, J.F., Singh, N.A., Dahle, E.J., Leppert, M.F., Pappas, C.M., Pruess, T.H., Wilcox, K.S., and White, H.S. (2009) Electroconvulsive Seizure Thresholds and Kindling Acquisition Rates are Altered in Mouse Models of Human KCNQ2 and KCNQ3 Mutations for Benign Familial Neonatal Convulsions. Epilepsia, 50(7):1752-1759.
Smeal, R.M., Keefe, K.A., and Wilcox, K.S. (2008) Differences in excitatory transmission between thalamic and cortical afferents to single spiny efferent neurons of dorsal striatum. Eur. J. Neurosci., 28(10):2041-2052.
Singh, N.A., Otto, J.F., Jill Dahle, E., Pappas, C., Leslie, J.D., Vilaythong, A., Noebels, J.L., White, H.S., Wilcox, K.S., and Leppert, M.F. (2008) Mouse models of human KCNQ2 and KCNQ3 mutations for benign familial neonatal convulsions show seizures and neuronal plasticity without synaptic reorganization. J Physiol., Jul 15;586(Pt 14):3405-3423. Epub 2008 May 15.
Libbey, J.E., Kirkman, N.J., Smith, M.C., Tanaka, T., Wilcox, K.S., White, H.S., and Fujinami, R.S. (2008) Seizures following picornavirus infection. Epilepsia, Jun;49(6):1066-74. Epub 2008 Mar 6. PMID: 18325012 [PubMed - indexed for MEDLINE]
White, H.S., Smith, M.D., and Wilcox, K.S. (2007) Mechanisms of action of antiepileptic drugs. Int Rev Neurobiol, 81:85-110.
Smith, M.D., Adams, A.C., Saunders, G.W., White, H.S., and Wilcox, K.S. (2007) Phenytoin- and carbamazepine-resistant spontaneous bursting in rat entorhinal cortex is blocked by retigabine in vitro. Epilepsy Res, May;74(2-3):97-106.
West, P.J., Dalpe-Charron, A., and Wilcox, K.S. (2007) Differential contribution of kainate receptors to excitatory postsynaptic currents in superficial layer neurons of the rat medial entorhinal cortex. Neuroscience, 146(3):1000-1012.
Smeal, R.M., Gaspar, R.C., Keefe, K.A., and Wilcox, K.S. (2007) A rat brain slice preparation for characterizing both thalamostriatal and corticostriatal afferents. J Neurosci Methods, Jan 30;159(2):224-35. Epub 2006 Aug 8.
Alex, A.B., Baucum, A.J., and Wilcox, K.S. (2006) Effect of Conantokin G on NMDA receptor-mediated spontaneous EPSCs in cultured cortical neurons. J. Neurophys., Sep;96(3):1084-1092.
Simeone, T.A., Wilcox, K.S., and White, H.S. (2006) Subunit selectivity of topiramate modulation of heteromeric GABAA receptors. Neuropharm., 50(7):845-857.
Otto, J.F., Yang, Y., Frankel, W.N., White, H.S., and Wilcox, K.S. (2006) A Spontaneous Mutation Involving Kcnq2 (Kv7.2) Reduces M Current Density and Spike Frequency Adaptation in Mouse CA1 Neurons. J. Neurosci., 26(7):2053-2059.
Otto, J.F., Yang, Y., Frankel, W.N., Wilcox, K.S., and White, H.S. (2004) Mice carrying the szt1 mutation exhibit increased seizure susceptibility and altered sensitivity to compounds acting at the m-channel. Epilepsia, Sep;45(9):1009-1016.
Barton, M.E., White, H.S., and Wilcox, K.S. (2004) The effect of CGX-1007 and CI-1041, novel NMDA receptor antagonists, on NMDA receptor-mediated EPSCs. Epilepsy Res., Mar;59(1):13-24.
Kaplan, M.P., Wilcox, K.S., and Dichter, M.A. (2003) Differences in multiple forms of short-term plasticity between excitatory and inhibitory hippocampal neurons in culture. Synapse, Oct;50(1):41-52.
Aaron, G.B., Wilcox, K.S., and Dichter, M.A. (2003) Different Patterns of Synaptic Transmission Revealed Between Distinct Classes of CA3 Hippocampal Interneurons and Their Pyramidal Cell Targets. Neuroscience 117:169-181.
Chapman, D.E., Keefe, K.A., and Wilcox, K.S. (2003) Electrophysiological Evidence for Functionally Distinct NMDA Receptors in Medial versus Lateral Striatum. J. Neurophys., 89:69-80.
Otto, J.F., Kimball, M., and Wilcox, K.S. (2002) Effects of the Anticonvulsant Retigabine on Cultured Cortical Neurons: Changes in Electroresponsive Properties and Synaptic Transmission. Molecular Pharmacology 61:921-927.