The long-term goal of this research is to understand the genetic basis of animal behavior. The approach is to study the function of the excitable cells that produce feeding behavior, the neurons and muscles of the Caenorhabditis elegans pharynx. In this grant period we will investigate plasticity in feeding behavior. The hypotheses to be tested are: Hypothesis 1. Worms assess the quality of their food. Hypothesis 2. Worms determine whether to seek new food by comparing the quality of their current food with past experience. Hypothesis 3. Worms conditioned on two foods learn to recognize and prefer the higher quality food. Hypothesis 4. Pharyngeal muscarinic acetylcholine receptors activated in response to low quality food increase feeding via a signal transduction pathway that activates MAP kinase MPK-1. Hypothesis 5. By changing the activity of a set of proteins that includes the calcium-activated K+ channel SLO-1, the strength of specific synapses can be increased or decreased, resulting in modified behavior. These hypotheses will be tested through 4 specific aims:
Aim 1 : Characterize the behavioral mechanisms of food preference. Given a choice between two foods, worms will select the higher quality one. We will examine the effects of physical conditions and experience on food preference to learn how worms assess food quality and whether worms learn to recognize and choose high-quality food (hypotheses 1-3).
Aim 2 : Determine the signal transduction pathway by which muscarinic acetylcholine receptors influence feeding behavior. Normal worms compensate for low-quality food by accelerating feeding motions. Muscarinic acetylcholine receptors are necessary for this response. By studying the effects of drugs and mutations that affect signaling systems, we will determine the complete pathway, and determine how it affects feeding behavior (hypothesis 4).
Aim 3 : Determine how SLO-1 suppresses the M4-> terminal bulb muscle synapse. We will compare the properties of the synapse in wild type and slo-1 worms, and determine what features of SLO-1 are necessary for suppression of synaptic activity (hypothesis 5).
Aim 4 : Identify mutations that activate the M4->TB neuromuscular junction. We have completed a screen for mutants that have higher than normal terminal bulb muscle activity. We will determine which of these mutations activate the M4 NMJ (as slo-1 null mutations do) and identify the genes they affect (hypothesis 5). Health relevance: Abnormal excitable cell function lies at the root of many diseases, from addiction to neurological disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL046154-15
Application #
6849936
Study Section
Genetics Study Section (GEN)
Program Officer
Wang, Lan-Hsiang
Project Start
1991-04-05
Project End
2009-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
15
Fiscal Year
2005
Total Cost
$270,200
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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Avery, Leon (2014) A model of the effect of uncertainty on the C elegans L2/L2d decision. PLoS One 9:e100580
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Straud, Sarah; Lee, Inhwan; Song, Bomi et al. (2013) The jaw of the worm: GTPase-activating protein EAT-17 regulates grinder formation in Caenorhabditis elegans. Genetics 195:115-25
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Cheong, Mi Cheong; Lee, Hyoung-Joo; Na, Keun et al. (2013) NSBP-1 mediates the effects of cholesterol on insulin/IGF-1 signaling in Caenorhabditis elegans. Cell Mol Life Sci 70:1623-36
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Avery, Leon; You, Young-Jai (2012) C. elegans feeding. WormBook :1-23
You, Young-Jai; Avery, Leon (2012) Appetite Control: worm's-eye-view. Anim Cells Syst (Seoul) 16:351-356
Raizen, David; Song, Bo-Mi; Trojanowski, Nick et al. (2012) Methods for measuring pharyngeal behaviors. WormBook :1-13

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