Abstract

The research projects proposed in this application are concerned with two problems, both of which deal with cholinergic synaptic transmission. The first project uses alpha-bungarotoxin, alpha-mambatoxin and additional toxins which block activation of nicotinic acetylcholine receptors on nerve cells to determine the relationship between the receptor and the molecule which binds alpha-bungaratoxin. This project will be conducted first using clonal cell lines and later central nervous system tissue to study structure, metabolism and regulation of acetylcholine receptors on nerve. The second project uses a murine model of myasthenia gravis to address specific questions about the production of paralysis. Immunological, genetic, and morphological experiments will use our documented strain dependence of paralysis as a means of examining separately the various mechanisms which might cause paralysis. Neuromuscular junctions from high and low responder strains will be studied in vitro to determine effects of antibodies on receptor degradation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS013546-10
Application #
3395232
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1978-01-01
Project End
1986-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Hernandez, Caterina M; Kayed, Rakez; Zheng, Hui et al. (2010) Loss of alpha7 nicotinic receptors enhances beta-amyloid oligomer accumulation, exacerbating early-stage cognitive decline and septohippocampal pathology in a mouse model of Alzheimer's disease. J Neurosci 30:2442-53
Gupta, Swati; Kim, Se Y; Artis, Sonja et al. (2010) Histone methylation regulates memory formation. J Neurosci 30:3589-99
Heffron, Daniel S; Landreth, Gary E; Samuels, Ivy S et al. (2009) Brain-specific deletion of extracellular signal-regulated kinase 2 mitogen-activated protein kinase leads to aberrant cortical collagen deposition. Am J Pathol 175:2586-99
Alexander, Jon C; McDermott, Carmel M; Tunur, Tumay et al. (2009) The role of calsenilin/DREAM/KChIP3 in contextual fear conditioning. Learn Mem 16:167-77
Ahn, Hyung Jin; Hernandez, Caterina M; Levenson, Jonathan M et al. (2008) c-Rel, an NF-kappaB family transcription factor, is required for hippocampal long-term synaptic plasticity and memory formation. Learn Mem 15:539-49
Lubin, Farah D; Roth, Tania L; Sweatt, J David (2008) Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J Neurosci 28:10576-86
Samuels, Ivy S; Karlo, J Colleen; Faruzzi, Alicia N et al. (2008) Deletion of ERK2 mitogen-activated protein kinase identifies its key roles in cortical neurogenesis and cognitive function. J Neurosci 28:6983-95
Klann, Eric; Sweatt, J David (2008) Altered protein synthesis is a trigger for long-term memory formation. Neurobiol Learn Mem 89:247-59
Chwang, Wilson B; Arthur, J Simon; Schumacher, Armin et al. (2007) The nuclear kinase mitogen- and stress-activated protein kinase 1 regulates hippocampal chromatin remodeling in memory formation. J Neurosci 27:12732-42
Chwang, Wilson B; O'Riordan, Kenneth J; Levenson, Jonathan M et al. (2006) ERK/MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning. Learn Mem 13:322-8

Showing the most recent 10 out of 33 publications