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Dopaminergic and Serotonergic Signaling in the Interplay of Locomotion, Food-motivated Behavior and Feeding in Caenorhabditis elegans
This project aims to investigate the interaction and potential interference of two neurotransmitters on the nervous system of the nematode C. elegans and ultimately on its behavior. The nervous system of C. elegans has a well-established, conserved anatomy, consisting of two largely independent parts: the somatic nervous system, containing 282 neurons that control locomotion and sensory functions, and the 20 neuron pharyngeal nervous system, which controls feeding. These two systems are primarily linked by the extrasynaptic release of neurotransmitters such as dopamine (DA) and serotonin (5-HT), which play a central role in foraging. Dopaminergic and serotonergic signaling adjust locomotion and feeding behaviors to the metabolic state of the animal and to the availability of food, and are thus adaptive traits.
The project will uncover how DA and 5-HT orchestrate the complex interplay between the two parts of the nervous system, using advanced optogenetic and imaging techniques. Light-activated, isotype-specific GPCRs (optoXRs) will be optimized and/or developed and used to investigate the distinct and sometimes opposing roles of D1 and D2 type DA receptors, and of the main 5-HT receptor, in motor neurons, in neurons affecting locomotion and navigation, and in pharyngeal neurons. The work will combine the specific expertise of both labs in order to achieve a comprehensive understanding of functional coupling of the two parts of the nervous system, at the cellular and behavioral levels.
Our objectives are: 1) to analyze global behavioral responses to DA and 5-HT exposure, and to their acute, systemic release using optogenetics, during foraging, in the context of the respective other neuromodulator; 2) to measure whole-brain Ca²⁺ dynamics, assessing key neurons under DA and 5-HT stimulation; and 3) to understand the role of excitatory and inhibitory DA and 5-HT GPCR activation, following mapping of local neurotransmitter release and its postsynaptic effects. 4) To activate specific GPCRs, we will use optoXRs in neurons expressing DA or 5-HT receptors endogenously and 5) investigate how activation of these signaling pathways in the two parts of the nervous system controls / coordinates locomotion and/or feeding behavior.
In summary, this work will show how these essential neuromodulators influence different neuronal functions depending on their timing, localization and competitive interactions. We expect this work to provide comprehensive insights into the neuromodulatory control of nervous system interactions and to improve our understanding of GPCR-mediated signaling in invertebrate neurobiology.