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:

Review Articles:

Faingold C.L., Darin J. Knapp, Julia A. Chester, and Larry P. Gonzalez, Integrative Neurobiology of the Alcohol Withdrawal Syndrome - From Anxiety to Seizures, Alcohol. Clin. Exp. Res.28:268-278, 2004.
Faingold, C.L., Emergent Properties of CNS Neuronal Networks as Targets for Pharmacology: Application to Anticonvulsant Drug Action, Prog. Neurobiol. 72:55-85, 2004.

Publications:

Raisinghani, M. and Faingold, C.L., Neurons in the amygdala play an important role in the neuronal network mediating a clonic form of audiogenic seizures both before and after audiogenic kindling. Brain Res. 1032:131-140, 2005.

Raisinghani, M. and Faingold, C.L., Evidence for the perirhinal cortex as a requisite component in the seizure network following seizure repetition in an inherited form of generalized clonic seizures. Brain Res. 1048:(1-2):193-201, 2005.

Tupal, S. and Faingold, C.L., Evidence supporting a role of serotonin in modulation of sudden death induced by seizures in DBA/2 mice. Epilepsia (In Press) 2005.

Raisinghani, M. and Faingold, C.L., Pontine reticular formation neurons are implicated in the neuronal network for generalized clonic seizures which is intensified by audiogenic kindling. Brain Res. (In Press) 2006.Yang, L., C. Long, M. E. Randall and C.L. Faingold, Neurons in the periaqueductal gray are critically involved in the neuronal network for audiogenic seizures during ethanol withdrawal, Neuropharmacology, 44:275-281, 2003.

Raisinghani, M. and Faingold, C.L. Identification of the requisite brain sites in the neuronal network subserving generalized clonic audiogenic seizures. Brain Res. 967:113-122, 2003.

Raisinghani, M., Feng, H.J. and C.L. Faingold. Glutamatergic activation of the amygdala differentially mimics the effects of audiogenic seizure kindling in two substrains of genetically epilepsy-prone rats, Exp. Neurol. 183:516-522, 2003.

Spier, A.W., L.A. Toth and C.L. Faingold. Clinical patent ductus arteriosus in adult genetically epilepsy-prone rats. Comparative Medicine 55 (1): 85-91, 2005.

Book Chapter:

Faingold, C.L., The midbrain and audiogenic seizures. In: The Inferior Colliculus (J.A. Winer and C.E. Schreiner, Eds.) Springer, New York, 2005, pp. 603-625.

Abstracts:

Faingold, C.L. and M. Randall. Involvement of the hippocampus in ethanol withdrawal seizures. Alcoholism Clin. Exp. Res. 29 (S):95A, 2005.

Faingold, C.L. and L. Yang. The substantia nigra exerts a gating role in control of ethanol withdrawal seizures. Alcoholism Clin. Exp. Res. 28 (S5):141A, 2004.

Faingold, C.L., M. Raisinghani, S. Tupal and M. Randall. A role of serotonin in modulating respiratory arrest in a model of sudden death in epilepsy (SUDEP) in DBA/2 mice. Epilepsia 45(Suppl 7):207-208, #2.048, 2004.

Tupal, S., M. Randall, M. Raisinghani and C.L. Faingold. Neuromodulation of seizure-induced respiratory arrest in DBA/2 Mice. Soc. Neurosci. Abst. 30: #452.10, 2004.

N’Gouemo, N., M. Morad and C.L. Faingold. Upregulation of calcium channel current is associated with seizure susceptibility in the genetically epilepsy-prone rat (GEPR-3) inferior colliculus neurons. Soc. Neurosci. Abst. 30: #566.4, 2004.