A reduction in the efficacy of synaptic inhibition within a focus may result in the generation of epileptic neuronal discharge. My preliminary results suggest that in the CA3 region of the hippocampus synaptic inhibition acts to prevent synchronous firing by suppressing multi-synaptic excitatory connections between CA3 cells. The way in which epileptic activity can spread from a focus to tissue outside the focus in a seizure is less clear. Several events will occur in an area of the brain which is synaptically connected to an epileptic focus. (1) Afferent fibres will be intensely activated. (2) The level of extracellular potassium will rise. (3) Neurotransmitters which modify the susceptibility to seizure may be released. I intend to examine whether these factors can modify either inhibitory or excitatory synapses between CA3 hippocampal cells in a way which would assist the propagation of synchronous firing. Specific objectives of the research are: (1) to study synapses between CA3 cells by recording from both pre- and post-synaptic neurons. Excitatory synapses terminating on inhibitory neurons, will be investigated. A reduction in efficacy of these synapses would facilitate the propagation of synchrony. (2) to elicit focal synchronized discharge by local convulsant application in longitudinal slices cut from the CA3 region. The regulation of propagation will be examined. (3) to examine modifications of inhibitory or excitatory synaptic circuits by the neurotransmitters acetylcholine, and enkephalin and by increased extracellular potassium. (4) to determine whether persistent changes at synapses between CA3 cells are induced by intense stimulation of afferent fibers. The association pathway linking different hippocampal lamellae will be stimulated in longitudinal slices and septal inputs will be examined in slices containing both the septal nuclei and the hippocampus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29NS024678-03
Application #
3476770
Study Section
Neurology A Study Section (NEUA)
Project Start
1987-04-01
Project End
1992-08-31
Budget Start
1989-04-01
Budget End
1990-08-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027