In mammals, a circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus mediates daily rhythms in behavior and physiology. Individual SCN neurons fire rhythmically with near-24-hour periodicity. It is not known how these neurons communicate within the SCN network to produce synchronous circadian rhythmicity. Vasoactive intestinal polypeptide (VIP) and GABA, implicated in tissue level rhythms, may be required for rhythmicity in, or synchrony among, individual SCN neurons. Determining how these transmitters affect the rhythms of individual SCN neurons is critical to understanding how coordinated rhythmic output is generated by the SCN network. We will employ multi-electrode array technology to record firing rate rhythms of single SCN neurons, in conjunction with genetic and pharmacologic manipulations aimed at blocking or mimicking GABA and VIP signaling. These experiments will directly identify which SCN neurons have cell-autonomous pacemaking ability, and test whether GABA or VIP signaling is needed to maintain synchrony between them or drive their rhythmicity. Our findings will facilitate the development of novel drug interventions for the treatment of circadian rhythm disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31MH073302-02
Application #
6955876
Study Section
Special Emphasis Panel (ZRG1-F02A (20))
Program Officer
Curvey, Mary F
Project Start
2004-09-30
Project End
2006-09-29
Budget Start
2005-09-30
Budget End
2006-09-29
Support Year
2
Fiscal Year
2005
Total Cost
$28,111
Indirect Cost
Name
Washington University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Aton, Sara J; Huettner, James E; Straume, Martin et al. (2006) GABA and Gi/o differentially control circadian rhythms and synchrony in clock neurons. Proc Natl Acad Sci U S A 103:19188-93
Aton, Sara J; Herzog, Erik D (2005) Come together, right...now: synchronization of rhythms in a mammalian circadian clock. Neuron 48:531-4
Aton, Sara J; Colwell, Christopher S; Harmar, Anthony J et al. (2005) Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons. Nat Neurosci 8:476-83