Drug Action on Neuronal Network Function in Brain Disorders

This laboratory investigates brain function and how epilepsy, alcoholism, chronic pain and anticonvulsants alter this function.  The billions of neurons in the brain are organized into networks that produce both normal and abnormal function.  Epilepsy, alcoholism, and neuropathic pain produce abnormal neuronal network function, involving bran areas that are capable of undergoing major functional changes or neuroplasticity.  Epilepsy is the most common neurological disorder of brain networks in man, and a major devastating consequence is sudden unexpected death in epilepsy (SUDEP).  Alcoholism is a major health problem and the neurobiology of alcohol withdrawal is poorly understood.  Neuropathic pain involves abnormal responses to non-painful stimuli and the ran mechanisms involved require further research.  Current treatments do not adequately control these conditions.  SUDEP in patients involve breathing problems associated with seizures and we are investigating a mouse SUDEP model, evaluating drugs that may be useful in SUDEP prevention.  One major goal of the lab is to understand brain mechanisms that produce seizures and to identify anticonvulsant drugs which prevent abnormal brain activity without affecting normal function.  Many of these anticonvulsants are also effective in treating alcohol withdrawal and neuropathic pain.  We use electrophysiologic and neuropharmacologic techniques in intact behaving animals to examine these problems.  To better understand network functions in health and disease, we evaluate neurotransmitters, which govern neuronal excitability by giving drugs that modify transmitter action.  Brain surgery and computer-assisted single cell recording are methods we use to test the effects of drugs on brain network sites in conscious animals.  The experiments involve animals with genetically-based epilepsy and animals subject to ethanol withdrawal or neuropathic pain.  This research is identifying specific neuronal networks and specific neurotransmitters that are involved in these processes, which include GABA, glutamate, and serotonin.  These substances are normal neurotransmitters, but their effects are altered in these brain disorders.  Completion of these research goals will improve the understanding of the normal and abnormal function and improve the treatment of these neurological disorders.

Recent Publications

Tupal S. and Faingold CL. Audiogenic kindling induces plastic changes in the neuronal firing patterns in periaqueductal gray, Brain Res. 1377: 60-66, 2011.

Samineni V, Premkumar LS, and Faingold CL. Post-ictal analgesia in genetically epilepsy-prone rats is induced by audiogenic seizures and involves cannabinoid receptors in the periaqueductal gray, Brain Res. 1389:177-183, 2011.

Faingold CL, Tupal S, and Randall M. Prevention of seizure-induced sudden death in a chronic SUDEP model by semichronic administration of a selective serotonin reuptake inhibitor. Epilepsy Behav., 22:186-190, 2011.

Faingold CL, Randall M, Mhaskar Y, and Uteshev VV. Differences in serotonin receptor expression in the brainstem may explain the differential ability of a serotonin agonist to block seizure-induced sudden death in DBA/2 vs. DBA/1 mice. Brain Res., 1418:104-110, 2011.