Behavioural and Metabolic Characterization of NPR-9 and AIB Signaling Dynamics in Caenorhabditis Elegans
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Authors
Campbell, Jason
Date
Type
thesis
Language
eng
Keyword
Neuroscience , C. elegans , Locomotion , Behaviour , Metabolism , Molecular neuroscience , Genetics , NPR-9 , AIB
Alternative Title
Abstract
Caenorhabditis elegans inhabit heterogeneous environments and are often faced with
diverse environmental cues. The nematode must modulate behavioural and physiological
mechanisms to avoid aversive environmental conditions while favouring conditions that promote
growth. Therefore, organisms must detect environmental cues via sensory neurons, integrate
sensory evoked signals via interneurons, and modulate downstream pathways dependent on
environmental context. Internal cues, such as a well fed or starved condition, can also
reconfigure the neural circuitry. Interneuron AIB functions as an integration hub that integrates
sensory-evoked signals and fine-tunes locomotory behaviours.
Previous work has highlighted that galanin-like G-protein coupled neuropeptide receptor
NPR-9 and stimulatory glutamate gated cation channel receptor GLR-1 function in anterior
interneuron AIB. npr-9 loss-of-function and over-expression mutants display abnormal
spontaneous locomotion patterns. Hence, we evaluated npr-9 and AIB-specific glr-1 mutant
locomotory phenotypes in response to diverse environmental cues. We have shown that NPR-9
functions in concert with GLR-1 to regulate AIB activity. We also highlighted that overexpression
of npr-9 interferes with locomotory modulation suggesting that NPR-9 upregulation
inhibits the capacity of AIB to integrate environmental cues. This phenotype persists in the
context of starvation suggesting that NPR-9 and AIB are also required for internal cue dependent
modulation.
AIB regulation via NPR-9, serotonin gated chloride channel MOD-1, and tachykinin
GPCR TKR-2 also regulates lipid metabolism, likely via the control of glutamate release. In the
context of the locomotory circuit, glutamate release inhibits inter/motor neuron RIM via
inhibitory glutamate gated chloride channel receptor AVR-14. Transforming growth factor beta
(TGF-β) receptor homolog receptor DAF-1 has been found to function in RIM and is regulated
via glutamatergic signaling. Therefore, we evaluated the influence of AIB glutamate release on
daf-1 lipid phenotypes. We highlight that diverse receptors in AIB can influence lipid
metabolism and feeding behaviour, while the influence of starvation also appears to be integrated
by AIB in the regulation of the aforementioned phenotypes. Collectively, this thesis indicates
that interneuron AIB integrates diverse signals from sensory neurons to modulate an array of
behavioural and physiological signaling pathways dependent on internal and external cues.
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Attribution 3.0 United States
Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.