This laboratory investigates electrophysiologic and neuropharmacologic mechanisms that control brain function. The billions of neurons in the brain are organized into networks that produce both normal and abnormal functions, such as convulsive seizures. Seizures are an abnormality of brain function that can be caused by external factors, such as drug administration or withdrawal, and by neurological diseases. Epilepsy is the most common neurological disorder in man, afflicting millions. Current anticonvulsant drugs do not provide adequate seizure control without significant adverse effects. Alcoholism is a major health problem, and the neurobiology of alcohol withdrawal, which includes seizures, is poorly understood. Both epilepsy and alcoholism involve altered function of neuronal networks in sensorimotor integration. A major goal of this laboratory is to understand brain mechanisms that produce seizures and to help develop anticonvulsant drugs which affect abnormal brain activity without interfering with normal function. To better understand normal brain function, we examine neurotransmitters which mediate excitability by administering agents that modify transmitter action. Stereotaxic brain surgery and computer-assisted single cell recording are used to test the effects of drugs on specific brain regions in conscious animals. The intracellular mechanisms of these changes are evaluated using brain slices. The experiments involve animals with a genetic form of epilepsy and animals undergoing ethanol withdrawal, both of which are subject to seizures induced by sound. This research is identifying a specific neuronal network and specific neurotransmitters that are involved in these convulsive processes, which include excitatory and inhibitory amino acids. These amino acids are normal neurotransmitters, and their function is altered in epilepsy and during alcohol withdrawal.

   Future work will be focused on the intracellular mechanisms of these convulsive seizures and the actions of anticonvulsant drugs with novel mechanisms on these seizures. The realization of the research goals of this laboratory will hopefully improve the understanding of normal and abnormal brain function and improve the treatment of epilepsy and alcoholism.

SELECTED REFERENCES:

Recent Review Articles and Book Chapters (of 25 total):

Faingold, C.L. The Majchrowicz binge alcohol protocol - an intubation technique to study alcohol dependence in rats (Unit 9.28, Supplement 44). In: Current Protocols in Neuroscience (M. Rogawski, Ed.), John Wiley, (pp. 928.1-928.12), Chapter 9:Unit 9.28.1 (supplement 44) July, 2008.

Faingold, C.L. Electrical stimulation therapies for CNS disorders and pain are mediated by competition between different neuronal networks in the brain. Medical Hypotheses 71:668-681, 2008.

Faingold CL, Tupal S, Mhaskar Y, Uteshev VV. DBA mice as models of sudden unexpected death in epilepsy. IN: Sudden Death in Epilepsy: Forensic and Clinical Issue", (C. Lathers, P. Schraeder, M. Bungo, J. Leestma, editors), Taylor and Francis (In Press), 2009.

Faingold, C.L. Anticonvulsant drugs actions on seizure networks. In: Encyclopedia of Epilepsy Basic Research (P. Schwartzkroin, Ed.), Elsevier (In Press), 2009.

Book Editor:

Faingold, C.L. (Co-editor) - Brody’s Human Pharmacology – Molecular to Clinical, 5th Edition ( Lynn Wecker, Lynn Crespo, George Dunaway, Carl Faingold, Stephanie Watts, Eds.), Elsevier, 2009.

Recent Publications (of 102 total):

Tupal, S., Faingold, C.L., Evidence supporting a role of serotonin in modulation of sudden death induced by seizures in DBA/2 mice, Epilepsia 47(1):21-26, 2006.

Toth, L.A., Wang, J., Bosgraaf, C., Reichensberger, J., Hughes, L.F., Faingold, C.L., Sleep, temperature, activity, and prolactin phenotypes of genetically epilepsy-prone rats, Comp. Med. 56:413-426, 2006.

Long, C, Yang, L., Faingold, C.L, Evans, M.S., Excitatory amino acid receptor-mediated responses in periaqueductal gray neurons are increased during ethanol withdrawal, Neuropharmacology, 52:802-811, 2007.

Feng, H.-J., L. Yang, Faingold, C.L., Role of the amygdala in ethanol withdrawal seizures, Brain Res. 1141:65-73, 2007.

Feng, H.J., Faingold, C.L., The effects of chronic ethanol administration on amygdala neuronal firing and ethanol withdrawal seizures. Neuropharmacology 55: 648-653, 2008.3.

N'Gouemo, P., Faingold, C.L., Morad, M., Calcium channel dysfunction inferior colliculus neurons of the genetically epilepsy-prone rat. Neuropharmacology 56(3):665-675, 2009.

N'Gouemo, P., Yasuda, R.P., Faingold, C.L., Protein expression of small conductance calcium-activated potassium channels is altered in inferior colliculus neurons of the genetically epilepsy-prone rat. Brain Res 1270:107-111, 2009.

Tupal, S., Faingold, C.L., Precipitous Induction of Audiogenic Kindling by Activation of Adenylyl Cyclase in the Amygdala, Epilepsia (in revision), 2009.

Recent Abstracts (of 179 total):

Faingold, C.L., Tupal, S. Activation of cAMP in the amygdala increases ethanol withdrawal seizure severity. Alcoholism Clin Exp Res. 31:769, 2007.

Faingold, C.L., Tupal, S. Periaqueductal gray neurons exhibit enhanced firing in response to audiogenic kindling behavior in GEPR-9s. American Epilepsy Society 48:Abs. 3.086, Philadelphia, PA, Dec. 2007..

Faingold CL, Tupal S. Activation of cAMP in the amygdala increases ethanol withdrawal seizure severity. Alcoholism Clin Exp Res. 32(6):601, 2008.

Uteshev VV, Mhaskar Y, Gusev AG, Randall M, Faingold CL. Differences in serotonin (5-HT) receptor expression/function in DBA/2 and C57BL/6J mice: relationship with SUDEP. Soc. Neurosci. Abst. 33:449.13, 2008.

Faingold CL, Randall M, Tupal S, Uteshev VV. SUDEP Model in DBA Mice: Long-Term SUDEP Susceptibility and Modulation by Serotonin (5-HT) Epilepsia 49(#10):3.060 (Seattle, Washington), 2008.