2006 — 2011 |
Zars, Troy |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Molecular Neurobiology of Operant Place Conditioning in Drosophila @ University of Missouri-Columbia
Operant conditioning most faithfully reflects learning in the natural environment. This type of learning is demonstrated by conditioning in the several variations of the Skinner box. For example, a pigeon can be trained to peck a lit key to receive a food reward. Importantly, operant learning has been identified in quite diverse species, indicating this fundamental function of the brain is general and evolutionarily conserved. Despite advances in operant conditioning models and an early understanding of the molecular and neural systems important for this type of learning, the gap between theory and mechanism remains large. Taking advantage of the many tools available for neuroscience investigations in the fruit fly, Drosophila melanogaster, first attempts at closing that gap are proposed. A so-called heat-box will be used to determine gene function within neural circuitry important for temperature perception and operant conditioning in the fly. In this paradigm, individual flies are conditioned to avoid one half of a small chamber by associating that half with a temperature outside the preferred range. Preliminary results identified parts of the neural circuitry critical for sensing warm temperatures (i.e. neurons of the antennae and downstream neural pathways). Genes expressed in those neurons will be investigated for their function in temperature perception. Furthermore, as prior investigation has identified key molecular processes within parts of the neural structure termed the median bundle that are critical for memory formation, novel learning gene function will be examined in this and similar structures. This project will contribute to a growing understanding of the molecular and circuit logic of brain function in the relatively simple fly and will provide unique training opportunities for undergraduate and graduate students in the lab.
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2015 — 2017 |
Milescu, Lorin (co-PI) [⬀] Milescu, Mirela (co-PI) [⬀] Zars, Troy |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Brain Eager: Novel Thermo-Genetic Tools For Extrinsic Control of Neuronal Circuits @ University of Missouri-Columbia
Brains can be thought of as networks of circuits. The neurons that make up these circuits interact to control behavior, but how the neurons do this is currently an open question. New tools are needed to learn how neuron networks produce behavior. One promising strategy would be to construct molecular switches that could flip neurons between active and inactive states. This project will investigate the potential to engineer a special group of proteins to make them serve as molecular switches that respond to changes in temperature. The proteins will be put into specific brain neurons of flies, and the fly's behaviors will be monitored in response to temperature changes that activate and deactivate the neurons. The fly is an accessible experimental model for these studies, and, additionally, what is learned in the fly brain will have broad relevance to other animal brains. The project will involve undergraduate and graduate students in the research and will provide them with interdisciplinary training in biophysics, neurophysiology, and behavior. Tools developed in the project have the potential to be used to understand other organ systems and will be shared with the wider scientific community.
Individual Gustatory Receptor (GR) gene family members will be examined for temperature-dependent effects on nerve cell function. In one set of experiments, these GRs will be expressed in both sensory and non-sensory neurons in Drosophila melanogaster and tested for temperature responsiveness in heat-box behavioral assays. In a second set of experiments, natural- and chimeric-GRs will be expressed in Xenopus oocytes and COS cells and tested for temperature- and voltage-dependent kinetics of ionic current. Finally, natural- and chimeric-GRs will be expressed in sensory neurons in Drosophila and cultured cells and examined for physiological effects using live calcium imaging analysis.
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2017 — 2020 |
Zars, Troy King, Elizabeth |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Quantitative Genetics of Learning and Memory in Drosophila. @ University of Missouri-Columbia
There is adaptive value in the ability of animals to learn and remember based on experience. Understanding the genetics of natural variation that supports experience-dependent behavioral plasticity greatly expands our perspective on how variation in these traits arises within a species. Through a combination of molecular biological tools for examining and mapping genetic material and sophisticated behavioral assays, this research program identifies most or all of the large-impact positions on the chromosome, or loci, that affect learning and memory traits in a genetically tractable model organism, the fruit fly. The results advance our understanding of the mechanisms that underlie learning and memory in naturally varying populations. The project also provides research opportunities in neuroscience, genetics, and bioinformatics for high school, undergraduate, and graduate students, including students from groups generally under-represented in science and technology.
Selection experiments have shown that natural genetic variants can play a critical role in the evolution of learning and memory. However, attempts to link specific variants to the selected traits have largely failed. Novel genetic panels and behavioral paradigms for Drosophila melanogaster now make it possible to better understand natural variants that are important for these traits on a genomic scale. The objectives of this proposal are addressed through two specific aims. Aim 1: Fully characterize loci that are important for Place learning and memory. Aim 2: Determine whether specific genetic loci that impact Place learning and memory also influence Olfactory learning and memory. To achieve these aims, a newly developed high-resolution quantitative genetic panel is applied to a set of behavioral problems that have traditionally been examined separately and with different approaches. Different from previous work, this program examines learning and memory in both classical and operant conditioning paradigms to test the hypothesis that there are common core natural genetic variants that influence learning and memory in general. By identifying and validating key genetic variants that influence place and olfactory learning and memory, the proposed experiments significantly improve our understanding of the genetic underpinnings of learning and memory in natural populations. Results provide critical insights into the natural genetic variants that influence learning and memory in multiple contexts, and into the evolution of learning and memory.
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