This multidisciplinary research program combines various analytic techniques to investigate the synaptic physiology, biophysics, and biochemistry of epileptogenesis and the development of the epileptic process in mammalian brain. The goal is to apply new methods of selectively measuring excitability changes at excitatory synapses, second-messenger modulation of inhibitory synaptic transmission, and axonal sprouting in specific neural networks to determine whether key excitability defects in epileptic brain are mediated by use-dependent and potentially reversible mechanisms. The research tests specific hypotheses extending from the molecular to the structural levels of neural organization, and is based on three model systems. (1) Acute epileptogenesis, using hippocampal slice techniques, will be studied with a focus on the immediate role of use-dependent plastic properties of recurrent excitatory synapses in the CA3 subfield and on long-term potentiation in the generation of epileptiform activity. (2) Chronic focal epileptogenesis, using slices from kindled animals, will be studied to determine the functional consequences of aberrant mossy fiber growth during prolonged abnormal stimulation. (3) Inherited generalized epileptogenesis, using slices from epileptic mice with single-locus genetic mutations, will be studied to examine synaptic and biochemical mechanisms underlying network bursting, modulation of GABA- receptor-mediated inhibition, and aberrant axonal sprouting and neosynaptogenesis. A critical element of this research program is the high degree of interaction and collaboration, at both technical and conceptual levels, among the scientists who comprise the research team.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
2P01NS011535-18A2
Application #
3099369
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1978-06-01
Project End
1997-11-30
Budget Start
1993-01-08
Budget End
1993-11-30
Support Year
18
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030