Sayin, Sercan (2019): Characterization of aminergic neurons controlling behavioral persistence and motivation in Drosophila melanogaster. Dissertation, LMU München: Faculty of Biology |
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Abstract
Deprivation is at odds with survival. To obliterate their condition of hunger animals engage in costly foraging behavior. This conundrum demands unceasing integration of external sensory processing and internal metabolic monitors. Unsurprisingly, such critical behaviors are translated to strong impulses. If unchecked, however, impulsivity can trap animals in unfavorable behavioral states and prevent them from exploiting other valuable opportunities. Categorically, motivational mechanisms have been proposed as the conduit to comply with or decline a response to a strong impulse. Thus, motivation emerges as a critical determinant for observed animal behavioral variability at a given time. Although neuronal circuit diagrams may be deceptively static, neuromodulation can implement behavioral variability in the nervous systems. Bioamines, such as dopamine and norepinephrine, mediate modulatory impact on intrinsic motivational circuits that govern feeding and reward. Across model organisms, however, how animals integrate and update decision-making based on the current motivational and internal states are still poorly understood at the molecular and circuitry levels. Due to its extensive toolbox and amenable miniature nervous systems, Drosophila melanogaster is poised to enrich the current perspective for these concepts. For Drosophila melanogaster, certain odors are salient cues for long distance foraging events. To explore how starved flies make goal-directed decisions, I developed a novel spherical treadmill paradigm. Through the utilization of high-resolution behavioral analyses and tight control of, otherwise highly turbulent, odor delivery, I found that food-deprived flies tracked vinegar persistently even in the repeated absence of a food reward. Combining this behavioral paradigm with immediate neuronal manipulations revealed that this innate persistence recruited circuits that are traditionally linked with learning and memory in an internal state-dependent manner. TH+ cluster dopaminergic neurons, operators of punishment learning, and Dop1R2 signaling enabled this olfactory-driven persistence. Downstream of these dopaminergic neurons, a single mushroom body output neuron, MVP2 was crucial for persistence. MVP2 was necessary and sufficient to integrate hunger state as the underlying motivational drive for food-seeking persistence. Furthermore, I investigated how this strong impulse is counteracted when a fly reaches its goal, nutritious food. A change from odor tracking to food consumption demands the coordination of different sensory systems and motor control subunits. Norepinephrine is implemented in such global switches; such as fight or flight transitions. Using optogenetic manipulation, I demonstrated that the food-seeking drive was suppressed by, an insect norepinephrine analog, octopaminergic input, via VPM4 neurons. Being connected to MVP2 synaptically, which we showed using high-resolution tracing techniques, and a surrogate for feeding at the neuronal level, VPM4 neurons acted as the inhibitory brake on persistent odor tracking to allow feeding related behavior. As a culmination of novel paradigm development, thermo/optogenetic neuronal manipulations and connectomics, this work presents a neuronal microcircuit that recapitulates the alterations of animal behavior faithfully from odor tracking to olfactory suppression during feeding. Specific subsets of dopaminergic and octopaminergic neurons are found to be mediators of motivationally driven events. My findings provide fresh mechanistic insights on how multimodal integration can occur in the brain, how such systems are prone to the internal states, and offers several plausible explanations on how persistence emerges. Finally, this work might serve as a template to better understand the roles and the functional diversity of mammalian aminergic neurons.
Item Type: | Theses (Dissertation, LMU Munich) |
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Keywords: | Drosophila melanogaster; dopamine; foraging; goal-directed behavior; learning; mushroom body; octopamine; olfactory system; persistence |
Subjects: | 500 Natural sciences and mathematics 500 Natural sciences and mathematics > 570 Life sciences |
Faculties: | Faculty of Biology |
Language: | English |
Date of oral examination: | 16. May 2019 |
1. Referee: | Gompel, Nicolas |
MD5 Checksum of the PDF-file: | 21554810b28f5e6c2648b0a85ce203ca |
Signature of the printed copy: | 0001/UMC 26955 |
ID Code: | 25674 |
Deposited On: | 17. Mar 2020 15:00 |
Last Modified: | 23. Oct 2020 14:21 |