The Journal of Neuroscience, June 3, 2009, 29(22):7302-7314; doi:10.1523/JNEUROSCI.3429-08.2009
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Behavioral/Systems/Cognitive
Stimulation of Movement in a Quiescent, Hibernation-Like Form of Caenorhabditis elegans by Dopamine Signaling
Marta Maria Gaglia1,2 and
Cynthia Kenyon1,2
1Neuroscience Program and Department of Biochemistry and Biophysics, and 2Hillblom Center for the Biology of Aging, University of California, San Francisco, San Francisco, California 94158
Correspondence should be addressed to Dr. Cynthia Kenyon, Department of Biochemistry and Biophysics, University of California, San Francisco, MC2200, Mission Bay Genentech Hall Room S312D, 600 16th Street, San Francisco, CA 94158-2517. Email: cynthia.kenyon{at}ucsf.edu
One of the characteristics of animals in hibernation is reduced behavioral activity. The Caenorhabditis elegans dauer state is a hibernation-like state of diapause that displays a dramatic reduction in spontaneous locomotion. A similar dauer-like quiescent state is produced in adults by relatively strong mutations in the insulin/IGF-1 receptor homolog daf-2. In this study, we show that mutations affecting the neurotransmitter dopamine, which regulates voluntary movement in many organisms, can stimulate movement in dauers and dauer-like quiescent adults. Surprisingly, the movement of quiescent animals is stimulated by conditions that reduce dopamine signaling and also by conditions predicted to increase dopamine signaling. Reducing dopamine signaling is likely to stimulate movement by activating a foraging response also seen in nondauers after withdrawal of food. In contrast, the stimulation of movement by increased dopamine is much more pronounced in quiescent daf-2(–) dauer and dauer-like adult animals than in nondauaer animals. This altered response to dopamine is primarily attributable to activity of the FOXO (forkhead box O) transcription factor DAF-16 in neurons. We suggest that dauers and dauer-like quiescent adults may have underlying changes in the dopamine system that enable them to respond differently to environmental stimulation.
Received July 21, 2008;
revised March 31, 2009;
accepted April 6, 2009.
Correspondence should be addressed to Dr. Cynthia Kenyon, Department of Biochemistry and Biophysics, University of California, San Francisco, MC2200, Mission Bay Genentech Hall Room S312D, 600 16th Street, San Francisco, CA 94158-2517. Email: cynthia.kenyon{at}ucsf.edu