Douglas A. Coulter, PhD
Abramson Pediatric Research Building
3516 Civic Center Blvd.
Philadelphia, PA 19104-4318
Fax: (215) 590-4121
B.S. (Biology with honors)
Trinity College, Hartford, CT, 1980.
University of Rhode Island, 1983.
Boston University Marine Program, Marine Biological Laboratory, Woods Hole, MA, 1986.
Description of Research ExpertiseKEY WORDS:
epilepsy, hippocampus, circuit imaging, GABA receptors, thalamus
Epilepsy, neuronal excitability, CNS rhythm generation, circuit imaging, GABA receptors, development of neurotransmitter receptors and ion channels, synaptic function
Patch clamp recordings, extracellular and intracellular recordings, multicellular calcium imagign, voltage sensitive dye imaging, chloride imaging, multiphoton microscopy, confocal microscopy, immunohistochemistry, neuronal cell culture, transgenic animals, in vitro and in vivo recording techniques, optical recordings, EEG recordings.
My research interests center on understanding the cellular and molecular mechanisms underlying the development of epilepsy. Symptomatic seizure disorders such as temporal lobe epilepsy are among the most prevalent and least medically responsive forms of epilepsy. They are also among the most interesting. A presumably normal individual receives some injurious stimuli, which, at some distant time point results in the initiation of an epileptic state, characterized by recurrent spontaneous seizures. A better understanding these seizure-initiating mechanisms should facilitate development of enhanced therapeutic strategies to improve treatment, and perhaps eventually contribute to the development of a cure for epilepsy.
My laboratory uses physiological, functional imaging, anatomical, and molecular techniques to address experimental issues relevant to epilepsy. Physiologically, my colleagues and I use patch clamp, intracellular, and extracellular recording techniques in both in vitro and in vivo preparations of animal or human brain. In terms of functional imaging, we use multiphoton, confocal, and epifluorescence microscopy to record titme resolved changes in calcium, voltage, and chloride throughout circuits during activity. Anatomically, we use immunohistochemical and conventional staining techniques to characterize alterations occurring in the epileptic brain at a circuit level, including loss of populations of neurons, alterations in expression patterns of proteins, and axonal remodeling. The combination of these diverse experimental approaches provides a powerful, synergistic approach to better understand critical factors contributing to the initiation of the epileptic condition.
Selected PublicationsCohen, A.S., Lin, D.D., Quirk, G.L. and Coulter, D.A.: Dentate granule cell GABAA receptors in epileptic hippocampus: enhanced synaptic efficacy and altered pharmacology. European Journal of Neuroscience 17: 1607-1616, 2003.
Burton, D.Y., Cunxian, S., Fishbein, I., Hazelwood, S., Li, Q., Defelice, S., Connolly, J.M., Perlstein, I., Coulter, D.A., and Levy, R.J.: The incorporation of an Ion channel gene mutation associated with the Long QT syndrome (Q9E-hMiRPI) in a plasmid vector for site-specific arrhythmia gene therapy: In Vitro and In Vivo feasibility studies. Human Gene Therapy 14: 907-922, 2003.
Rafiq, A., Gong, Q.Z., Lyeth, B.G., DeLorenzo, R.J., and Coulter, D.A.: Induction of prolonged electrographic seizures in vitro has a defined threshold and is all or none: implications for diagnosis of status epilepticus. Epilepsia 44(8): 1034-1041, 2003.
Crino, P., Jin, H., Rikhter, T.Y, Robinson, M.B., Coulter, D.A., and Brooks Kayal, A.R.: Increased expression of the neuronal glutamate transporter (EAAT3/EAAC1) in hippocampal and neocortical epilepsy. Epilepsia 43(3): 211-218, 2002.
Gibbs III, J.W., Zhang, Y.-F., Ahmed, H.S., and Coulter, D.A.: Anticonvulsant actions of Lamotrigine on spontaneous thalamocortical rhythms. Epilepsia 43(4): 342-349, 2002.
Itoh, T., Beesley, J., Itoh, A., Kavanaugh, B., Cohen, A.S., Coulter, D.A., Grinspan, J.B., and Pleasure, D.: AMPA glutamate receptor-mediated calcium signaling is transiently enhanced during development of oligodendrocytes. Journal of Neurochemistry 81: 390-402, 2002.
Coulter, D.A., McIntyre, D.C., and Loscher, W.: Animal models of limbic epilepsies: What can they tell us? Brain Pathology 12: 240-256, 2002.