Biology Theses and Dissertations

Permanent URI for this collectionhttp://hdl.handle.net/1903/2749

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    SEROTONIN REGULATES AN OLFACTORY CRITICAL PERIOD IN DROSOPHILA
    (2024) Mallick, Ahana; Araneda, Ricardo; Gaudry, Quentin; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Serotonin (5-HT) is known to modulate early development during critical periods when experience drives heightened levels of plasticity in sensory systems. Studies in the somatosensory and visual cortices implicate multiple target points of serotonergic modulation, yet the underlying cellular and molecular mechanisms of 5-HT modulation of critical period plasticity remain elusive. Here, we take advantage of the genetically tractable olfactory system of Drosophila to investigate how 5-HT modulates critical period plasticity (CPP) in the CO2 sensing circuit of fruit flies. During the critical period, chronic exposure to CO2 has been shown to increase the volume of the CO2 sensing V glomerulus. We found that 5-HT release by serotonergic neurons in the antennal lobe (AL) is required for increase in the volume of the V glomerulus. Furthermore, signaling via the 5-HT1B, 5-HT2B and 5-HT7 receptors in different neuronal populations is also required during the critical period. Olfactory CPP is known to involve local inhibitory networks and consistent with this we found that knocking down 5-HT7 receptors in a subset of GABAergic local interneurons was sufficient to block CPP, as was knocking down GABA receptors expressed by olfactory sensory neurons (OSNs). Additionally, 5-HT2B expression in the cognate OSNs sensing CO2 is also essential for CPP indicating that direct modulation of OSNs also contributes to the olfactory CPP. Furthermore, 5-HT1B expression by serotonergic neurons in the olfactory system is also required during the critical period. Our study reveals that 5HT modulation of multiple neuronal targets is necessary for experience-dependent structural changes in an odor processing circuit. Finally, we wanted to isolate the neuromodulatory effects of individual serotonergic neurons. To achieve this, we combined a state-of-the-art technique to sparsely label serotonergic neurons and a computer algorithm to search against 10,000 Gal4 promoter lines and identify candidate lines that would allow individual manipulation of the 110 serotonergic neurons.
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    PHYSIOLOGICAL CHARACTERIZATION OF SPECIFIC LOCAL INTERNEURON SUBPOPULATIONS IN THE DROSOPHILA ANTENNAL LOBE
    (2022) Schenk, Jonathan Edward; Gaudry, Quentin; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    The olfactory system of the fruit fly Drosophila melanogaster is an invaluable model for understanding circuit function. Composed mainly of olfactory receptor neurons (ORNs), projection neurons (PNs), and local interneurons (LNs), it is an analogous structure to mammalian olfactory systems. Of these cell types, LNs are particularly intriguing. These neurons are found in a variety of morphologies and with differing neurotransmitter and receptor profiles. Given their heterogeneity, it is critical to gain an understanding of their roles in olfactory circuits. In this work, I probe the physiology and functions of two unique subpopulations of LNs in the antennal lobe (AL). In the first population, I demonstrate LNs which respond to extrasynaptic, paracrine levels of serotonergic modulation. These LNs then engage in postsynaptic inhibition and subtractive gain control, which is contrary to typical LNs. The second population I characterize are previously undescribed nonspiking LNs in the fly AL. Nonspiking cells are common to insect olfaction as well as other sensory pathways in vertebrates. I find that these neurons are likely to be electrotonically compartmentalized, such that activation within individual regions does not propagate across the whole cell, suggesting roles in previously unexplained mechanisms such as intraglomerular inhibition. The results of this work suggest more heterogeneity in Drosophila LNs than previously assumed and cements the importance of interneuron contribution to neuronal function.
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    Comparative transcriptomics of long intergenic noncoding RNAs in Drosophila
    (2015) Nyberg, Kevin Glenn; Machado, Carlos A; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Without the constraints of the amino acid code, long intergenic noncoding RNAs (lincRNAs) can be expected to evolve along different trajectories than protein-coding genes. Most studies of lincRNA evolution analyze evolution only at the sequence level without ascertaining whether the lincRNA is expressed. Over 2,000 lincRNAs (and counting) have already been identified in the classic model system Drosophila melanogaster. Here, using RNA-Seq and computational identification of protein-coding ability, we identify 1,768 lincRNA transcripts at 1,586 unique loci in a second species of Drosophila - D. pseudoobscura. These lincRNAs are expressed in every surveyed developmental stage (1st instar larva, 3rd instar larva, pupa, and adult) in both sexes, with a large number increasing in expression as male development proceeds. This male bias can largely be explained by overrepresentation of lincRNAs in the testes. Unequal distributions of sex-biased lincRNAs on the X chromosome and autosomes are consistent with selection-based models of gene trafficking on or off the X chromosome, implying function for some of these lincRNAs. Finally, reciprocal blast searches between annotated lincRNAs in the D. pseudoobscura and D. melanogaster transcriptomes identify 80 conserved lincRNAs. Interestingly, direct coordinate conversions between the two genomes reveal another 54 D. pseudoobscura lincRNAs that are expressed in the same position as a D. melanogaster lincRNA but have low enough sequence conservation to preclude alignment via blast. Whether these positionally equivalent lincRNAs are true homologs with similar functions in both genomes is unclear, but we look at other transcript features, such as transcript orientation, gene structure, and developmental expression profiles to explore this possibility. We find 22 high-confidence lincRNA homologs with conservation of multiple transcript-level features, and we designate these as high-confidence homologs that warrant further biological investigation. This work represents the first comparative transcriptomic analyses of lincRNAs in Drosophila.