The cerebral cortex has the ability to generate rhythmic synchronized network activity both in the form of normal neural rhythms as well as during epileptic seizures. A key cell type in the generation of these patterns of synchronized activity is burst generating neurons. Intrinsically bursting pyramidal cells with extensive local axon collaterals have been described previously in layer V, and more recently in layers II-III. Recent work ha shown that a class of these neurons, called chattering cells, have the ability to generate sustained high frequency (30-70 Hz) burst firing. However, the mechanisms by which these cells generate burst discharges, or the functional influences of these burst discharges on post-synaptic neurons, is not presently known. Preliminary studies have shown that chattering cells have a prominent single spike after-depolarization (AD), and each burst is followed by a large after-depolarization (AHP). In addition, some non-chattering cells can be induced to chatter by addition of cholinergic or metabotropic glutamate receptor agonists, or by prolonged depolarization. In this project we intend to use intracellular recording in an in vitro slice preparation of ferret visual cortex with the following specific aims: 1. To investigate the ionic mechanisms of the spike ADP in chattering cells, and its role in generating high frequency burst firing. 2. To investigate the ionic mechanisms of the post-burst AHP in chattering cells, and its role in determine the frequency of burst generation. 3. To investigate the mechanism for inducing non-chattering cells with neuromodulators or depolarization to fire repetitive high frequency bursts. 4. To use dual cell recording to study the effects of high frequency burst firing on synaptic transmission. The information provided by these studies may yield insights into the mechanisms of normal cortical rhythmic oscillations, and suggest new therapies for the therapeutic management of epileptic seizures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
2K08NS002060-04
Application #
6334612
Study Section
NST-2 Subcommittee (NST)
Program Officer
Jacobs, Margaret
Project Start
1998-07-01
Project End
2003-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
4
Fiscal Year
2001
Total Cost
$132,300
Indirect Cost
Name
Yale University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520