STUDIES OF HUMAN EPILEPTIC CORTEX IN VITRO

Project: Research project

Project Details

Description

Epilepsy is a neurological disorder affecting many people. However, for
ethical and technical reasons, research aimed at understanding the basic
mechanisms underlying the epileptiform disorder has been carried out
primarily with various animal models of epilepsy. These studies have
provided considerable information about how abnormal discharge might arise,
but the relevance of these data to epilepsy, as it occurs in human
patients, is often unclear. The in vitro slice preparation offers us a
method whereby electrophysiological, morphological, and pharmacological
access to human epileptic tissue is facilitated. We propose to continue our studies of human epileptic tissue using this in
vitro technique. Slices (600 um thick) of human temporal cortex will be
made from tissue removed during neurosurgical procedures for intractable
epilepsy. Cells from both lateral and mesial temporal cortex will be
studied using intracellular techniques. We will characterize the passive
and synaptic properties of each cell (i.e., input resistance, resting
potential, action potential parameters, cellular response to stimulation)
and attempt to correlate these measures with cellular morphology by
injecting cells with intracellular labels. Special attention will be
focused on cellular bursting activity and presence of inhibitory
postsynaptic potentials (IPSPs). Recent slice studies of human tissue have
yielded evidence of spontaneous rhythmic synchronous events (SRSEs) in some
tissue samples; the basis for such activity will be investigated using
simultaneous intracellular recordings (to study synchrony) and various ion
blockers (to evaluate underlying synaptic mechanisms). The tissue will
also be challenged with excitatory agents (high potassium concentration,
GABA blockers) to see if epileptogenic properties can be uncovered,
accentuated, or attenuated. Finally, single cell electrophysiology and
morphology will be related to general tissue pathology. These studies will provide descriptive and mechanistic information about
abnormal cellular properties in human epileptic tissue, information that
will help us to better define the epileptic focus. In addition, such
cellular studies will act as a bridge by which we can interpret and relate
data from experimental models of epilepsy to cellular activity in human
epileptic brain.
StatusFinished
Effective start/end date7/1/856/30/88

Funding

  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.