Abstract

The objective of this proposal is to continue a comprehensive research program focused on study of mechanisms of limbic epilepsy. The proposal brings together investigators with skills in molecular neurobiology, electrophysiology, anatomy, pharmacology, and clinical epilepsy. These skills will be focused on tests of alternative hypotheses advanced to explain the hyperexcitability of limbic epilepsy. These alternative hypotheses will be tested in a diversity of preparations including animal models in vivo as well as a diversity of reduced in vitro preparations, some of which have been isolated from the rodents in which epilepsy has been induced. The work is centered in particular on the excitability of two principal neuronal populations, the dentate granule cells and CA3 pyramidal cells. Successful completion of the work proposed promises to shed light on the mechanisms underlying limbic epilepsy. Such insights will hopefully lead to new and more effective therapies and perhaps prevent development of this disorder. Insights into normal hippocampal circuitry and how it is modified following brain injury and pathologic activity will also emerge from this work, this promises to aid understanding of a diversity of nervous system disorders in addition to limbic epilepsy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
2P01NS017771-19
Application #
6093300
Study Section
Special Emphasis Panel (ZNS1-SRB-W (01))
Program Officer
Jacobs, Margaret
Project Start
1995-05-15
Project End
2005-04-30
Budget Start
2000-06-05
Budget End
2001-04-30
Support Year
19
Fiscal Year
2000
Total Cost
$1,408,817
Indirect Cost

  Institution

Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Crooks, Kristy R; Kleven, Daniel T; Rodriguiz, Ramona M et al. (2010) TrkB signaling is required for behavioral sensitization and conditioned place preference induced by a single injection of cocaine. Neuropharmacology 58:1067-77
Nadler, J Victor; Tu, Bin; Timofeeva, Olga et al. (2007) Neuropeptide Y in the recurrent mossy fiber pathway. Peptides 28:357-64
Jiao, Yiqun; Nadler, J Victor (2007) Stereological analysis of GluR2-immunoreactive hilar neurons in the pilocarpine model of temporal lobe epilepsy: correlation of cell loss with mossy fiber sprouting. Exp Neurol 205:569-82
He, X-P; Butler, L; Liu, X et al. (2006) The tyrosine receptor kinase B ligand, neurotrophin-4, is not required for either epileptogenesis or tyrosine receptor kinase B activation in the kindling model. Neuroscience 141:515-20
Bausch, Suzanne B; He, Shuijin; Petrova, Yelena et al. (2006) Plasticity of both excitatory and inhibitory synapses is associated with seizures induced by removal of chronic blockade of activity in cultured hippocampus. J Neurophysiol 96:2151-67
Tu, B; Jiao, Y; Herzog, H et al. (2006) Neuropeptide Y regulates recurrent mossy fiber synaptic transmission less effectively in mice than in rats: Correlation with Y2 receptor plasticity. Neuroscience 143:1085-94
Timofeeva, Olga; Nadler, J Victor (2006) Facilitation of granule cell epileptiform activity by mossy fiber-released zinc in the pilocarpine model of temporal lobe epilepsy. Brain Res 1078:227-34
Tu, Bin; Timofeeva, Olga; Jiao, Yiqun et al. (2005) Spontaneous release of neuropeptide Y tonically inhibits recurrent mossy fiber synaptic transmission in epileptic brain. J Neurosci 25:1718-29
Danzer, Steve C; McNamara, James O (2004) Localization of brain-derived neurotrophic factor to distinct terminals of mossy fiber axons implies regulation of both excitation and feedforward inhibition of CA3 pyramidal cells. J Neurosci 24:11346-55
Danzer, Steve C; He, Xiaoping; McNamara, James O (2004) Ontogeny of seizure-induced increases in BDNF immunoreactivity and TrkB receptor activation in rat hippocampus. Hippocampus 14:345-55

Showing the most recent 10 out of 219 publications