Abstract

This Program Project has a central theme-the role of lipids, particularly eicosanoids, as neurotransmitters, intracellular second messengers and modulators of synaptic plasticity. We have identified through previous work and preliminary studies both biochemical and electrophysiological evidence that supports a role for these lipids in neural signaling. In the process, we have identified new neural lipid metabolic pathways and metabolites, 8(R)-lipoxygenase and 8-KETE, identified """"""""unusual"""""""" nicotine acetylcholine receptors with sequence similarity to prostaglandin receptors, and identified strong links between lipid metabolism and synaptic plasticity in models of LTP and LTD in the mammalian hippocampus and in components in eicosanoid biochemistry, neural physiology and molecular biology. These methods are combined to address three major efforts: 1) What is the role of lipid modulators in long-term synaptic plasticity? 2) What is the role of lipid metabolites in presynaptic facilitation by nicotine? 3) Are eicosanoids pheromones in mammals? These Units are composed of investigators from 5 independent laboratories and are supported by a Core Unit devoted to lipid biochemistry.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS029832-09
Application #
6330452
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Leblanc, Gabrielle G
Project Start
1992-05-01
Project End
2002-11-30
Budget Start
2000-12-01
Budget End
2001-11-30
Support Year
9
Fiscal Year
2001
Total Cost
$934,724
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Pharmacology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032

  Publications

Besana, Alessandra; Robinson, Richard B; Feinmark, Steven J (2005) Lipids and two-pore domain K+ channels in excitable cells. Prostaglandins Other Lipid Mediat 77:103-10
Unni, Vivek K; Zakharenko, Stanislav S; Zablow, Leonard et al. (2004) Calcium release from presynaptic ryanodine-sensitive stores is required for long-term depression at hippocampal CA3-CA3 pyramidal neuron synapses. J Neurosci 24:9612-22
Cohen-Armon, Malka; Visochek, Leonid; Katzoff, Ayelet et al. (2004) Long-term memory requires polyADP-ribosylation. Science 304:1820-2
Feinmark, Steven J; Begum, Roxana; Tsvetkov, Evgeny et al. (2003) 12-lipoxygenase metabolites of arachidonic acid mediate metabotropic glutamate receptor-dependent long-term depression at hippocampal CA3-CA1 synapses. J Neurosci 23:11427-35
Guan, Zhonghui; Kim, Joung-Hun; Lomvardas, Stavros et al. (2003) p38 MAP kinase mediates both short-term and long-term synaptic depression in aplysia. J Neurosci 23:7317-25
Leypold, Bradley G; Yu, C Ron; Leinders-Zufall, Trese et al. (2002) Altered sexual and social behaviors in trp2 mutant mice. Proc Natl Acad Sci U S A 99:6376-81
Tieman, T L; Steel, D J; Gor, Y et al. (2001) A pertussis toxin-sensitive 8-lipoxygenase pathway is activated by a nicotinic acetylcholine receptor in aplysia neurons. J Neurophysiol 85:2150-8
Du, C; Role, L W (2001) Differential modulation of nicotinic acetylcholine receptor subtypes and synaptic transmission in chick sympathetic ganglia by PGE(2). J Neurophysiol 85:2498-508
Barazangi, N; Role, L W (2001) Nicotine-induced enhancement of glutamatergic and GABAergic synaptic transmission in the mouse amygdala. J Neurophysiol 86:463-74
Scott, K; Brady Jr, R; Cravchik, A et al. (2001) A chemosensory gene family encoding candidate gustatory and olfactory receptors in Drosophila. Cell 104:661-73

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