Neurotrophins play critical roles in the development of the nervous system by promoting neuronal survival and differentiation. These factors have also been implicated in the pathophysiologic mechanisms underlying Alzheimer's and other neurodegenerative diseases. At the cellular level, neurotrophins play a dynamic role in modulating synaptic transmission in the hippocampus, a brain structure of particular interest because of its proposed role in learning and memory processes as well as its selective vulnerability to injury. This research project uses electrophysiological approaches to characterize the molecular targets and signaling cascades underlying neurotrophin-induced synaptic plasticity. Recent evidence has demonstrated specific biochemical effects of neurotrophins on glutamate receptors, mediated by activation of trkB tyrosine kinase receptors in postsynaptic membranes. The proposed studies will examine the physiological context of these novel neurotrophin effects. The proposed studies will examine the physiological context of these novel neurotrophin effects, focusing specifically on functional modulation of glutamate receptor activity. Initial experiments use neuronal cultures and patch-clamp recordings to characterize the regulation of channel kinetics and elucidate underlying protein kinase signaling cascades. Later studies will explore neurotrophin modulation within the more complex cellular environment of hippocampal slices, investigating the roles of neurotrophins in synaptic plasticity and neuronal-glial interactions. These studies will contribute to a broader understanding of neurotrophin action in the brain, with potential therapeutic applications in neurogenerative disease.

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 #
5R29NS039167-03
Application #
6330602
Study Section
Special Emphasis Panel (ZRG1-MDCN-5 (01))
Program Officer
Sheehy, Paul A
Project Start
1998-12-25
Project End
2003-11-30
Budget Start
2000-12-01
Budget End
2001-11-30
Support Year
3
Fiscal Year
2001
Total Cost
$89,550
Indirect Cost
Name
University of Connecticut
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030