Brain Research Institute

Istvan Mody, Ph.D.

Email Address:
mody@ucla.edu

Work Address:
Laboratory
635 Charles Young Dr S
Los Angeles, CA 90095
UNITED STATES

Office
635 Charles Young Dr S
Los Angeles, CA 90095
UNITED STATES

Work Phone Number:
(310) 206-3484
310-206-4481

Department / Division Affiliations

Professor, Neurology

Member, ACCESS Program: Dept. of Molecular, Cell & Integrative Physiology, Neuroengineering Training Program, Neuroscience IDP, Brain Research Institute

Faculty, Molecular, Cellular, and Integrative Physiology IDP, Biomedical Engineering IDP

Bio:

Synaptic Signaling in Health and Disease Our research focuses on 1) the physiology, pharmacology, and pathology of synaptic transmission in the mammalian brain, and 2) the regulation of intracellular calcium homeostasis. The two themes ultimately converge in our quest for understanding how long-term alterations in the excitability of nerve cells and circuits are responsible for offsetting the frail balance between excitation and inhibition. Tipping this balance, either acutely of chronically, results in the nervous system showing signs of abnormal activity leading to specific brain disorders. We study synaptic transmission and the activation of extrasynaptic receptors in the healthy and the diseased brain. We presently carry out research in animal models of epilepsy, Huntington's disease, stress, alcoholism, PMS/PMDD, postpartum depression, while also recording from human brain tissue surgically removed for the treatment of epilepsies. By studying the fundamental mechanisms responsible for the altered synapses and circuits our studies will lead to novel therapies for a number of devastating neurological and psychiatric disorders. The experimental approaches we use include patch-clamp recordings (whole-cell, single channel and perforated patch) in brain slices, in acutely isolated animal and human neurons, or in cultured neurons/slices; chronic recordings in vivo to monitor long-term changes in the excitability of circuits; infrared and fluorescent video microscopy and simultaneous recordings in live brain tissue; various neuroanatomical and immunohistochemical techniques; measurement of intraneuronal calcium and the binding kinetics of calcium to various calcium-binding proteins; molecular biological approaches aimed at reducing or altering specific brain proteins as in genetic knockouts/knockins and various methods aimed at altering cellular protein levels.

Publications:

Mann, E.O. and Mody, I. The multifaceted role of inhibition in epilepsy: seizure-genesis through excessive GABAergic inhibition in ADNFLE. Curr. Opin. Neurol. 2008; 21: 155-160.

Glykys, J., Peng, Z., Chadra, D., Homanics, G.E., Houser, C.R. and Mody, I. A novel naturally occurring GABAA receptor subunit partnership with high sensitivity to ethanol. Nature Neuroscience 2007; 10: 40-48.

Faas, G.C., Schwaller, B., Vergara, J.L., and Mody, I. Resolving the fast kinetics of cooperative binding: Ca2+ buffering by calretinin . PLoS Biol 2007; 5: 2646-2660.

Glykys, J. and Mody, I. The activation of GABAA receptors: the view from outside the synaptic cleft. Neuron 2007; 56: 763-770.

Klaasen, A., Glykys, J., Maguire, J.L., Labarca, C., Mody, I. and Boulter, J. Seizures and enhanced cortical GABAergic inhibition in two mouse models of human autosomal dominant nocturnal frontal lobe epilepsy. Proc. Natl. Acad. Sci. USA 2006; 103: 19152-19157.

Maguire, J.L., Stell, B.M., Rafizadeh, M. and Mody, I. Ovarian cycle-linked changes in GABAA receptors mediating tonic inhibition alter seizure susceptibility and anxiety.. Nature Neuroscience 2005; 8: 797-804.

Mody, I. and Pearce, R.A. Interneuron diversity series: Diversity of inhibitory neurotransmission through GABAA receptors.. Trends in Neurosci. 2004; 27: 569-575.

Stell, BM Brickley, SG Tang, CY Farrant, M Mody, I Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by delta subunit-containing GABAA receptors.. Proceedings of the National Academy of Sciences of the United States of America. . 2003; 100(24): 14439-44.