| A Neuronal Signaling Pathway of CaMKII and Gqα Regulates Experience-Dependent Transcription of tph-1. | |
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MedLine Citation:
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PMID: 23325232 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Dynamic serotonin biosynthesis is important for serotonin function; however, the mechanisms that underlie experience-dependent transcriptional regulation of the rate-limiting serotonin biosynthetic enzyme tryptophan hydroxylase (TPH) are poorly understood. Here, we characterize the molecular and cellular mechanisms that regulate increased transcription of Caenorhabditis elegans tph-1 in a pair of serotonergic neurons ADF during an aversive experience with pathogenic bacteria, a common environmental peril for worms. Training with pathogenic bacteria induces a learned aversion to the smell of the pathogen, a behavioral plasticity that depends on the serotonin signal from ADF neurons. We demonstrate that pathogen training increases ADF neuronal activity. While activating ADF increases tph-1 transcription, inhibiting ADF activity abolishes the training effect on tph-1, demonstrating the dependence of tph-1 transcriptional regulation on ADF neural activity. At the molecular level, the C. elegans homolog of CaMKII, UNC-43, functions cell-autonomously in ADF neurons to generate training-dependent enhancement in neuronal activity and tph-1 transcription, and this cell-autonomous function of UNC-43 is required for learning. Furthermore, selective expression of an activated form of UNC-43 in ADF neurons is sufficient to increase ADF activity and tph-1 transcription, mimicking the training effect. Upstream of ADF, the Gqα protein EGL-30 facilitates training-dependent induction of tph-1 by functional regulation of olfactory sensory neurons, which underscores the importance of sensory experience. Together, our work elucidates the molecular and cellular mechanisms whereby experience modulates tph-1 transcription. |
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Authors:
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Yuqi Qin; Xiaodong Zhang; Yun Zhang |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 33 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-01-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 925-35 Citation Subset: IM |
Affiliation:
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Departments of Organismic and Evolutionary Biology and Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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