GSBS Dissertations and Theses

Date of Completion

3-28-2013

Document Type

Doctoral Dissertation

Academic Program

Neuroscience

Department

Department of Neurobiology; Alkema Lab

First Thesis Advisor

Mark J. Alkema

Keywords

Caenorhabditis elegans, ion channels, transmitters, escape behavior

Subjects

Dissertations, UMMS; Caenorhabditis elegans; Ion Channels; Neurotransmitter Agents; Tyramine; Escape Reaction

Abstract

Despite the current understanding that sensorimotor circuits function through the action of transmitters and modulators, we have a limited understanding of how the nervous system directs the flow of information necessary to orchestrate complex behaviors. In this dissertation, I aimed to uncover how the nervous system coordinates these behaviors using the escape response of the soil nematode, Caenorhabditis elegans, as a paradigm. C. elegans exhibits a robust escape behavior in response to touch. The worm typically moves forward in a sinusoidal pattern, which is accompanied by exploratory head movements. During escape, the worm quickly retreats by moving backward from the point of stimulus while suppressing its head movements. It was previously shown that the biogenic amine tyramine played an important role in modulating the suppression of these head movmemetns in response to touch. We identified a novel tyramine-gated chloride channel, LGC-55, whose activation by tyramine coordinates motor programs essential for escape. Furthermore, we found that changing the electrical nature of a synapse within the neural circuit for escape behavior can reverse its behavioral output, indicating that the C. elegans connectome is established independent of the nature of synaptic activity or behavioral output. Finally, we characterized a unique mutant, zf35 , which is hyperactive in reversal behavior. This mutant was identified as a gain of function allele of the C. elegans P/Q/N-type voltage-gated calcium channel, UNC-2. Taken together, this work defines tyramine as a genuine neurotransmitter and completes the neural circuit that controls the initial phases of the C. elegans escape response. Additionally, this research further advances the understanding of how the interactions between transmitters and ion channels can precisely regulate neural circuit activity in the execution of a complex behavior.

Comments

This dissertation includes 16 videos that are referenced in Chapters II, III, and IV. See Additional Files below.

Rights and Permissions

Copyright is held by the author, with all rights reserved.

Movie II-1.mov (3743 kB)
Movie of a wild-type animal on plates containing 30 mM tyramine.

Movie II-2.mov (2713 kB)
Movie of a wild-type animal after 5 minutes on plates containing 30 mM tyramine.

Movie II-3.mov (1470 kB)
Movie of a lgc-55 animal after 5 minutes on plates containing 30 mM tyramine.

Movie II-4.mov (1148 kB)
Movie of gentle anterior touch response of wild-type animals.

Movie II-5.mov (744 kB)
Movie of gentle anterior touch response of lgc-55(tm2913) mutant animals.

Movie II-6.mov (678 kB)
Movie of gentle anterior touch response of transgenic animals expressing glr-1::LGC-55.

Movie II-7.mov (1154 kB)
Movie of gentle anterior touch response of transgenic animals expressing myo-3::LGC-55.

Movie III-1.mov (116487 kB)
Movie of a wild-type animal on a plate containing 30 mM tyramine.

Movie III-2.mov (71135 kB)
Movie of LGC-55 LM2 on a plate containing 30 mM tyramine.

Movie III-3.mov (82805 kB)
Movie of gentle anterior touch response of wild-type animals.

Movie III-4.mov (73732 kB)
Movie of gentle anterior touch response of LGC-55 LM2 animals.

Movie III-5.mov (31500 kB)
Movie of wild-type animals expressing ptdc-1::ChR2 in response to blue light.

Movie III-6.mov (25200 kB)
Movie of LGC-55 LM2 animals expressing ptdc-1::ChR2 in response to blue light.

Movie IV-1.mov (68404 kB)
Movie of wild-type animals on food.

Movie IV-2.mov (60904 kB)
Movie of zf35 animals on food.

Movie IV-3.mov (68404 kB)
Movie of e55 animals on food.

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