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 n layers II-III. Recent work has 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 influence of these burst discharges on postsynaptic neurons, is not presently known. Preliminary studies have shown that chattering cells have a prominent single spike afterdepolarization (ADP), and each burst is followed by a large afterhyperpolarization (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 determining the frequency of burst generation. 3. To investigate the mechanisms 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 important 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 #
5K08NS002060-02
Application #
2891481
Study Section
NST-2 Subcommittee (NST)
Program Officer
Jacobs, Margaret
Project Start
1998-07-01
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Yale University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520