We have isolated clones encoding the members of the nicotinic acetylcholine receptor (nAChR) gene family, sequenced these clones, determined the loci in the rat brain of the cells that express the genes encoding these sequences, expressed these clones in the Xenopus oocyte to form functional neuronal nAChRs, and have discovered several interesting and unanticipated properties of the expressed receptors and of their synthesis. We also have used these clones, other new reagents we have created, and our knowledge of the properties of these receptors to address issues of their composition, assembly, disposition on the cell surface, and role in synapse formation. In the studies we are now proposing we will use the reductionist approach that has characterized our ongoing 30-year research endeavor, and for this phase of our studies focus intently on one specific nAChR subtype: the alpha7 nAChR. In our studies of the alpha7 nAChR we will focus on its physiologic roles, mechanisms of action, and its potential contribution to neurological disorders. In our studies we will ask the following questions: What are the hippocampal signal transduction mechanisms to which alpha7 nAChRs couple? What is the role of alpha7 nAChRs in the regulation of gene expression in the hippocampus? What is the role of the alpha7 nAChRs system in amyloid-beta peptide toxicity and Alzheimer's disease? These experiments are motivated by our new appreciation of the diversity of the ligand-gated ion channels and are designed to move our study of the neuronal nAChRs from the clones that encode them to the properties of the expressed proteins and their roles in synaptic function and modification in the central nervous system.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Special Emphasis Panel (ZRG1)
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Talley, Edmund M
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Baylor College of Medicine
Schools of Medicine
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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

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