Epilepsy is a major neurologic public health problem which affects and estimated 4 million persons in this country. Despite its prevalence and research efforts which span several decades, knowledge of the cellular mechanisms of epilepsy remains limited. The proposes research will investigate the cellular mechanisms of kindling, a major model of epilepsy. In particular, we propose to investigate the relationship between kindling and long-term patentiation (LTP) of synaptic transmission in the hippocampal formation. It is now well recognized that kindling involves transsynaptic changes, although the precise nature of these changes is uncertain. Two major hypotheses have been proposed for the transsynaptic alteration. One possible mechanisms is LTP, which refers to the enhancement of synaptic transmission which occurs when high frequency trains of stimulation are applied to certain hippocampal structures. the second mechanism is neurochemical alterations which enhance synaptic transmission. We propose to investigate the relatinship of kindling and LTP with the following two major questions: 1) Is kindling in the hippocampal formation accompanied by a permanent increase in synaptic transmission (i.e. LTP)? 2) Is LTP a necessary and sufficient condition for the development of kindling? These questions will be addressed with chronic microrecording techniques in unrestrained, unanesthetized rats who will receive a variety of stimulation paradigms which induce a state of permanent epileptogenesis. The proposal tests the relationship between LTP and kindling and attempts to define better the transsynaptic changes which occur during epileptogenesis. If we determine that LTP is not a mechanism of kindling, the result will, nevertheless, be important, as it will focus attention on the 2nd mechanism, namely neurochemical changes

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07NS000808-05
Application #
3078180
Study Section
Neurological Disorders Program Project Review B Committee (NSPB)
Project Start
1984-07-01
Project End
1989-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715