Abstract

The objective of this proposal is to carry out a comprehensive research program focused on the study of basic mechanisms of limbic epilepsy. The proposal brings together investigators with expertise in anatomy, biochemistry, pharmacology, physiology, and clinical epilepsy. These skills will be focused on studies of both the kindling and kainic acid models of epilepsy in the rat. The proposal also includes characterization of some physiologic processes in hippocampal formation, namely dendritic inhibition and spike frequency adaptation, and will assess whether alterations of these fundamental processes are involved in epilepsy. Biochemical and morphologic studies will be performed on hippocampal formation surgically removed from humans with medically intractable complex partial epilepsy. The ultimate goal of all components of this proposal is to further our understanding of the basic mechanisms of epilepsy from study of model systems. This information should provide a rational basis for new pharmacologic approaches designed to more effectively treat or prevent human epilepsy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS017771-08
Application #
3099698
Study Section
(SRC)
Project Start
1982-05-01
Project End
1990-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Duke University
Department
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