Behavioural and Metabolic Characterization of NPR-9 and AIB Signaling Dynamics in Caenorhabditis Elegans

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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