Electrical activity in circadian clock neurons plays an important role in cellular oscillation. However, the particular voltage-gated ionic conductances necessaryfor circadian function and the mechanisms by which electrochemical signals interact with transcriptional events in the nucleus of clock neurons remain unknown. To identify the particular ionic conductances necessary for cellular oscillation, ion channel subtype-specific membrane-tethered toxins are transgenically expressed in clock neurons to interfere with voltage-gated conductances. Preliminary studies reveal substantial effects of in vivo expression of Ca2+ and K+ channel tethered toxin blockers on free-running behavioral rhythms. The proposed aims are (1) to test dose- dependence of these behavioral effects, (2) to examine effects of tethered toxins on cellular oscillation, and (3) to determine the molecular identities of the blocked ion channels. The long-term goal of this proposal is to improve understanding of circadian clock function, an issue of substantial health relatedness, given the great costs to society of genetic and environmental disruption of human sleep/wake cycles.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS055527-03
Application #
7367935
Study Section
Special Emphasis Panel (ZRG1-F02A-H (20))
Program Officer
Mitler, Merrill
Project Start
2006-03-01
Project End
2009-02-28
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
3
Fiscal Year
2008
Total Cost
$55,852
Indirect Cost
Name
Yale University
Department
Physiology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Wu, Ying; Cao, Guan; Pavlicek, Beth et al. (2008) Phase coupling of a circadian neuropeptide with rest/activity rhythms detected using a membrane-tethered spider toxin. PLoS Biol 6:e273