Abstract

Ca2+/calmodulin-sensitive adenylyl cyclases (AC) are likely to be important for various types of synaptic plasticity. Transgenic mice deficient for type 1 adenylyl cyclase (I-AC) are deficient in certain types of spatial learning. Biochemical analysis of these mice indicate that the brain may contain at least one other Ca2+/calmodulin-sensitive AC. The long-term goals of this proposal are to determine if Ca2+/calmodulin-dependent ACs are required for LTP or spatial learning, determine which genes are in cultured primary neurons are regulated by cAMP, and determine if the Ca2+/calmodulin- sensitive ACs contribute to Ca2+ regulation of gene expression in cultured neurons. The sensitivity of IX-AC to CaM and Ca2+ will also be investigated.
The specific aims of this project include the determination of the necessity of I-AC, III-AC and VIII-AC for specific forms of LTP or LTD and determining if the Ca2+/CaM sensitivity of I-AC is crucial for LTP and/or spatial learning. Furthermore, the investigator proposes to isolate the clone for IX-AC, determine if AC activity in neurons is regulated by membrane potential, determine what genes in cultured hippocampal neurons are regulated by cAMP, determine which forms of LTP activate CRE-mediated transcription, and determine if Ca2+/calmodulin-sensitive ACs contribute to regulation of gene expression in cultured neurons.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020498-16
Application #
2883617
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Michel, Mary E
Project Start
1984-04-01
Project End
2000-02-29
Budget Start
1999-03-01
Budget End
2000-02-29
Support Year
16
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Pharmacology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Luo, Jie; Chen, Xuanmao; Pan, Yung-Wei et al. (2015) The type 3 adenylyl cyclase is required for the survival and maturation of newly generated granule cells in the olfactory bulb. PLoS One 10:e0122057
Wang, Wenbin; Pan, Yung-Wei; Zou, Junhui et al. (2014) Genetic activation of ERK5 MAP kinase enhances adult neurogenesis and extends hippocampus-dependent long-term memory. J Neurosci 34:2130-47
Chen, Ying-Zhang; Friedman, Jennifer R; Chen, Dong-Hui et al. (2014) Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia. Ann Neurol 75:542-9
Saraf, Amit; Luo, Jie; Morris, David R et al. (2014) Phosphorylation of eukaryotic translation initiation factor 4E and eukaryotic translation initiation factor 4E-binding protein (4EBP) and their upstream signaling components undergo diurnal oscillation in the mouse hippocampus: implications for memory per J Biol Chem 289:20129-38
Wardlaw, Sarah M; Phan, Trongha X; Saraf, Amit et al. (2014) Genetic disruption of the core circadian clock impairs hippocampus-dependent memory. Learn Mem 21:417-23
Luo, Jie; Phan, Trongha X; Yang, Yimei et al. (2013) Increases in cAMP, MAPK activity, and CREB phosphorylation during REM sleep: implications for REM sleep and memory consolidation. J Neurosci 33:6460-8
Hwang, Christopher K; Chaurasia, Shyam S; Jackson, Chad R et al. (2013) Circadian rhythm of contrast sensitivity is regulated by a dopamine-neuronal PAS-domain protein 2-adenylyl cyclase 1 signaling pathway in retinal ganglion cells. J Neurosci 33:14989-97
Pan, Yung-Wei; Storm, Daniel R; Xia, Zhengui (2013) Role of adult neurogenesis in hippocampus-dependent memory, contextual fear extinction and remote contextual memory: new insights from ERK5 MAP kinase. Neurobiol Learn Mem 105:81-92
Xia, Zhengui; Storm, Daniel R (2012) Role of signal transduction crosstalk between adenylyl cyclase and MAP kinase in hippocampus-dependent memory. Learn Mem 19:369-74
Chen, Xuanmao; Xia, Zhengui; Storm, Daniel R (2012) Stimulation of electro-olfactogram responses in the main olfactory epithelia by airflow depends on the type 3 adenylyl cyclase. J Neurosci 32:15769-78

Showing the most recent 10 out of 88 publications