Browsing by keyword "neural circuits"
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A conserved neuropeptide system links head and body motor circuits to enable adaptive behaviorNeuromodulators promote adaptive behaviors that are often complex and involve concerted activity changes across circuits that are often not physically connected. It is not well understood how neuromodulatory systems accomplish these tasks. Here, we show that the Caenorhabditis elegans NLP-12 neuropeptide system shapes responses to food availability by modulating the activity of head and body wall motor neurons through alternate G-protein coupled receptor (GPCR) targets, CKR-1 and CKR-2. We show ckr-2 deletion reduces body bend depth during movement under basal conditions. We demonstrate CKR-1 is a functional NLP-12 receptor and define its expression in the nervous system. In contrast to basal locomotion, biased CKR-1 GPCR stimulation of head motor neurons promotes turning during local searching. Deletion of ckr-1 reduces head neuron activity and diminishes turning while specific ckr-1 overexpression or head neuron activation promote turning. Thus, our studies suggest locomotor responses to changing food availability are regulated through conditional NLP-12 stimulation of head or body wall motor circuits.
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Neural Circuit Analyses of the Olfactory System in Drosophila: Input to Output: A DissertationThis thesis focuses on several aspects of olfactory processing in Drosophila. In chapter I and II, I will discuss how odorants are encoded in the brain. In both insects and mammals, olfactory receptor neurons (ORNs) expressing the same odorant receptor gene converge onto the same glomerulus. This topographical organization segregates incoming odor information into combinatorial maps. One prominent theory suggests that insects and mammals discriminate odors based on these distinct combinatorial spatial codes. I tested the combinatorial coding hypothesis by engineering flies that have only one class of functional ORNs and therefore cannot support combinatorial maps. These files can be taught to discriminate between two odorants that activate the single functional class of ORN and identify an odorant across a range of concentrations, demonstrating that a combinatorial code is not required to support learned odor discrimination. In addition, these data suggest that odorant identity can be encoded as temporal patterns of ORN activity. Behaviors are influenced by motivational states of the animal. Chapter III of this thesis focuses on understanding how motivational states control behavior. Appetitive memory in Drosophilaprovides an excellent system for such studies because the motivational state of hunger promotes reliance on learned appetitive cues whereas satiety suppresses it. We found that activation of neuropeptide F (dNPF) neurons in fed flies releases appetitive memory performance from satiety-mediated suppression. Through a GAL4 screen, we identified six dopaminergic neurons that are a substrate for dNPF regulation. In satiated flies, these neurons inhibit mushroom body output, thereby suppressing appetitive memory performance. Hunger promotes dNPF release, which blocks the inhibitory dopaminergic neurons. The motivational drive of hunger thus affects behavior through a hierarchical inhibitory control mechanism: satiety inhibits memory performance through a subset of dopaminergic neurons, and hunger promotes appetitive memory retrieval via dNPF-mediated disinhibition of these neurons. The aforementioned studies utilize sophisticated genetic tools for Drosophila. In chapter IV, I will talk about two new genetic tools. We developed a new technique to restrict gene expression to different subsets of mushroom body neurons with unprecedented precision. We also adapted the light-activated adenylyl cyclase (PAC) from Euglena gracilis as a light-inducable cAMP system for Drosophila. This system can be used to induce cAMP synthesis in targeted neurons in live, behaving preparations.
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Neuroendocrine Modulation of Complex Behavior and Physiology in C. elegansTo survive, animals must adapt to a complex and challenging world in a way that is flexible and responsive, while maintaining internal homeostasis. Neuromodulators provide a means to systemically alter behavioral or physiological state based on intrinsic or extrinsic cues, however dysregulated neuroendocrine signaling has negative consequences for fitness and survival. Here I examine neuroendocrine function and dysfunction using the escape response in Caenorhabditis elegans. The RFamide neuropeptide FLP-18 is a co-transmitter with the monoamine tyramine and functions both synergistically and antagonistically to tyramine in coordinating escape behavior. Using behavioral analysis and calcium imaging, I show that FLP-18 functions primarily through the G-protein coupled receptor (GPCR) NPR-5 to increase calcium levels in muscle, enhancing locomotion rate, bending and reversal behavior during the escape response. Furthermore, I examine the relationship between persistent acute stress and resilience using repeated activation of the escape response as a model of neuroendocrine dysregulation. Repeated activation of the escape response shortens lifespan and renders animals more susceptible to thermal, oxidative, and nutritional stress. Tyramine release is necessary and sufficient for this effect and activity of the tyraminergic RIM neurons is differentially regulated by acute versus long-term stressors. Impaired stress resistance requires both the GPCR TYRA-3 in the intestine and intestinal neuropeptide release. Activation of the insulin receptor DAF-2 is downstream of TYRA-3 and inhibits the transcription factors DAF-16/FOXO, SKN-1/Nrf2 and HSF-1, linking monoamine signaling in acute stress to the insulin signaling pathway and impaired resilience to long-term stressors.
