Please cite this article as follows: Zubenko GS, Jones ML, Estevez AO, Hughes III HB, Estevez M. 2009. Identification of a CREB-Dependent Serotonergic Pathway and Neuronal Circuit Regulating Foraging Behavior in Caenorhabditis elegans: A Useful Model for Mental Disorders and Their Treatments? Am J Med Genet Part B 150B:12–23.
Identification of a CREB-dependent serotonergic pathway and neuronal circuit regulating foraging behavior in Caenorhabditis elegans: A useful model for mental disorders and their treatments?†
Article first published online: 25 NOV 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 150B, Issue 1, pages 12–23, 5 January 2009
How to Cite
Zubenko, G. S., Jones, M. L., Estevez, A. O., Hughes, H. B. and Estevez, M. (2009), Identification of a CREB-dependent serotonergic pathway and neuronal circuit regulating foraging behavior in Caenorhabditis elegans: A useful model for mental disorders and their treatments?. Am. J. Med. Genet., 150B: 12–23. doi: 10.1002/ajmg.b.30891
- Issue published online: 21 JAN 2009
- Article first published online: 25 NOV 2008
- Manuscript Accepted: 8 OCT 2008
- Manuscript Received: 2 SEP 2008
- National Research Service Award from the National Institute of Mental Health. Grant Number: T32 MH18273
- Research Career Development Award from the Veterans Administration
- Burroughs Welcome Fund Career Award in the Biomedical Sciences
- National Institute of Mental Health. Grant Number: MH47346
- animal model;
- major depression;
The cAMP-response element binding protein (CREB)-mediated cell signaling pathway is conserved through evolution and participates in a broad range of complex behaviors of divergent species including man. This study describes the integration of genetic, pharmacologic, and anatomic methods to elucidate a serotonergic signaling pathway by which the CREB homolog CRH-1 controls foraging rate (FR) in the model organism Caenorhabditis elegans, along with the complete neuronal circuit through which this pathway operates. In the anterior afferent arm of the circuit, CRH-1 controls FR by regulating the expression of tph-1, the sole structural gene for tryptophan hydroxylase, in serotonergic sensory (ADF) neurons whose post-synaptic effects are mediated through 5HT2-like SER-1 receptors. The posterior afferent limb of the circuit includes an interneuron (RIH) that does not express tph-1 and whose serotonergic phenotype is dependent on the contribution of this neurotransmitter from another source, probably the ADF neurons. The postsynaptic effects of the RIH interneuron are mediated through 5HT1-like SER-4 receptors. This model has potential utility for the study of clinical disorders and experimental therapeutics. Furthermore, the discovery of serotonergic neurons that depend on other sources for their neurotransmitter phenotype could provide a mechanism for rapidly altering the number and distribution of serotonergic pathways in developing and adult nervous systems, providing a dimension of functional complexity that has been previously unrecognized. © 2008 Wiley-Liss, Inc.