Barrow Neurological Institute - Home
Contact Us Career Opportunities Advanced Search Search Tips
About Barrow Physician Directory Medical Specialities, Centers and Clinics Research and Clinical Trials Patient and Family Information Education Information
Research and Clinical Trials
Basic Research Laboratories
Neural Physiology Laboratory
Laboratory Focus
Major Research Accomplishments
Team Members
Print this page Email this page Change text size
Barrow Neurological Institute


Neural Physiology Laboratory Focus



Nicotinic Acetylcholine Receptor (nAChR) Physiology, Pharmacology, and Pathophysiology

Our laboratory studies the function and pharmacology of recombinant nicotinic acetylcholine receptors (nAChRs) transfected into a cloned cell line (the SH-EP1 cell line) and natively expressed nAChRs in neurons of the central nervous system using patch-clamp whole-cell and single-channel recordings.  By combining electrophysiology and molecular techniques, we systematically evaluate the diversity of nAChR subunits and function.  Ongoing projects include the following:

(1) Molecular mechanisms of nicotinic acetylcholine receptor dependence (DA015389: Co-I)

(2) VTA nicotinic receptors and nicotine dependence (IMHR Pilot grant: PI, ABRC Research Grant: PI)

(3) Development of pharmacotherapies for nicotine addiction (U19-DA019377: Co-I)

(4) Nicotinic receptors involved in mood and reward (Philip Morris External Research Grant: Co-I)

Patch-clamp recordings (current-clamp mode) in freshly dissociated
cells from human hypothalamic hamartoma tissue.

 

Cellular and Molecular Mechanisms of Epilepsy

We study the cellular and molecular mechanisms of epileptogenesis in different epilepsy animal models and epilepsy patient brain tissues.  We use state-of-the-art electrophysiological techniques (intracellular recordings from brain slices and patch-clamp recordings from acutely dissociated and cultured neurons) combined with cellular and molecular biological methods.  Ongoing projects include the following:

(1) Epileptogenesis of human hypothalamic hamartoma (The Women's Board of the Barrow Neurological Foundation, NBI: PI, NIH NS056104: PI)

(2) Cellular and molecular mechanisms of epileptogenesis in a model of acquired absence epilepsy induced by blockade of cerebral cholesterol synthesis

(3) Cellular and molecular mechanisms of epileptogenesis in generalized convulsive status epilepticus (in collaboration with David Treiman, MD, Director, Epilepsy Center, Barrow Neurological Institute)

(4) Cellular and pharmacological mechanisms of ketogenic diet in prevention and treatment of epilepsy (in collaboration with Jong M. Rho, MD, Associate Director, Division of Child Neurology, Director, Pediatric Epilepsy Research, Barrow Neurological Institute).


Cellular Mechanisms of Neurodegeneration

(1) Effects of MPP+ (or rotenone) toxin on dopamine neuron degeneration.  This project is designed to elucidate neuronal (dopaminergic) receptor/channel functions during acute MPP+ perfusion in single, isolated dopamine neurons under patch-clamp recordings.  This study will enhance our understanding of dopaminergic neuron degeneration induced by neurotoxins and provide novel experimental evidence for the prevention and treatment of Parkinson?s disease.

(2) Interaction between amyloid-beta peptides and nAChRs.  Accumulating lines of evidence indicate that there is a significant increase in the amount of amyloid-beta peptides in the brain of patients with Alzheimer's disease (AD), and that amyloid-beta peptide deposition and aggregation are the important mechanisms responsible for the genesis and development of AD.  This project evaluates the interaction between amyloid-beta peptides and nAChRs and will provide novel insights leading to a more complete understanding of the roles of nAChRs in the pathogenesis of AD.  It also may provide new strategies for therapy and prevention of AD.

(3) Physiology, pharmacology, and pathophysiology of ATP-sensitive K+ channels.