The ability to switch between different forms of locomotion is critical to many
aspects of survival, whether it is switching from walking to running to evade predators, or
switching to a slower gait to obtain food. Uncovering the mechanisms behind gait
transitions has implications for many fields, from treating Parkinson Disease to
understanding the impact of drugs of abuse on movement. However, the mechanisms of
gait transitions are not well understood. The experiments outlined in this thesis sought to
understand the neuronal basis for gait switching. This work employed the nematode
Caenorhabditis elegans, a unique model organism chosen for its genetic tractability and
fully characterized nervous system.
C. elegans displays different forms of motion: crawling on land and swimming
in liquid. First, I sought to determine the mechanisms for switching between these forms
of motion in collaboration with Dr. Andres Vidal-Gadea. In the process, we discovered
that crawling and swimming actually represent distinct gaits in contrast to recent reports
that suggested they were merely a single gait. We further elucidated mechanisms for gait
transition in C. elegans. For instance, we found that the transition to crawling required
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the D1-like dopamine receptors DOP-1 and DOP-4; and activation of dopamine neurons
via the light-activated cation channel Channelrhodopsin2 was sufficient to induce
crawling behavior in worms immersed in liquid. Conversely, photoactivation of
serotonergic neurons expressing Channelrhodopsin2 induced swim-like behavior on land.
Finally, laser microablation of dopaminergic or serotonergic neurons was sufficient to
impair the transition to crawl or swim, respectively. Together these results show that
transitions to crawling and swimming are controlled by dopamine and serotonin
respectively.
Next I wanted to better understand how gait transitions are impaired by a drug of
abuse, alcohol. I found that, as in other organisms, ethanol disrupts gait transitions,
causing worms in water to inappropriately transition from swim to crawl and to display
other land-specific behaviors. Animals lacking the D1-like dopamine receptor DOP-1
were resistant to the ethanol-induced transition to crawl. Finally, I found that several
interneurons required for the transition to crawl. Specifically, laser microablation of the
DOP-4 receptor-expressing neuron RID or the DOP-1-expressing neurons PQR or RIS
resulted in a significant impairment in the time to crawl onset. Overall, the findings
presented in this thesis represent the first evidence that C. elegans uses an evolutionarily
conserved mechanism to transition between gaits and provides the beginning of a
molecular description of gait transitions. / text
| Identifer | oai:union.ndltd.org:UTEXAS/oai:repositories.lib.utexas.edu:2152/23188 |
| Date | 17 February 2014 |
| Creators | Topper, Stephen Matthew |
| Source Sets | University of Texas |
| Language | en_US |
| Detected Language | English |
| Format | application/pdf |
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