Date

8-4-2011

UMMS Affiliation

Graduate School of Biomedical Sciences, Program in Neuroscience

Document Type

Dissertation, Doctoral

Subjects

Dissertations, UMMS; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Escape Reaction; Locomotion; Tyramine; Receptors, Biogenic Amine

Disciplines

Neuroscience and Neurobiology

Abstract

An animal’s ability to navigate through its natural environment is critical to its survival. Navigation can be slow and methodical such as an annual migration, or purely reactive such as an escape response. How sensory input is translated into a fast behavioral output to execute goal oriented locomotion remains elusive. In this dissertation, I aimed to investigate escape response behavior in the nematode C. elegans. It has been shown that the biogenic amine tyramine is essential for the escape response. A tyramine-gated chloride channel, LGC-55, has been revealed to modulate suppression of head oscillations and reversal behavior in response to touch. Here, I discovered key modulators of the tyraminergic signaling pathway through forward and reverse genetic screens using exogenous tyramine drug plates. ser-2, a tyramine activated G protein-coupled receptor mutant, was partially resistant to the paralytic effects of exogenous tyramine on body movements, indicating a role in locomotion behavior. Further analysis revealed that ser-2 is asymmetrically expressed in the VD GABAergic motor neurons, and that SER-2 inhibits neurotransmitter release along the ventral nerve cord. Although overall locomotion was normal in ser-2 mutants, they failed to execute omega turns by fully contracting the ventral musculature. Omega turns allow the animal to reverse and completely change directions away from a predator during the escape response. Furthermore, my studies developed an assay to investigate instantaneous velocity changes during the escape response using machine based vision. We sought to determine how an animal accelerates in response to a mechanical stimulus, and subsequently decelerates to a basal locomotion rate. Mutant analysis using this assay revealed roles for both dopamine and tyramine signaling. During my doctoral work, I have further established the importance for tyramine in the nematode, as I have demonstrated two additional roles for tyramine in modulating escape response behavior in C. elegans.

Comments

This dissertation includes 9 videos that are referenced in Chapters II, III, and IV. See Additional Files below.

Movie 2-1.avi (81618 kB)
Wild-type animals on 30 mM tyramine

Movie 3-1.avi (3479 kB)
Immobilized wild-type animal on 30 mM exogenous tyramine

Movie 3-2.avi (4294 kB)
Resistant ser-2 mutant animal on 30 mM exogenous tyramine

Movie 3-3.mov (11294 kB)
VD ablated animal

Movie 3-4.mov (8499 kB)
DD ablated animal

Movie 3-5.m4v (2423 kB)
Acute activation and inhibition of DD motor neurons using 109 light-gated proteins

Movie 3-6.avi (5442 kB)
Wild-type omega turn after gentle anterior touch

Movie 3-7.avi (4863 kB)
ser-2 omega turn after gentle anterior touch

Movie 4-1.avi (5603 kB)
C. elegans escape response during a vibrational stimulus