Browsing by Subject "Neurotransmitter Agents"
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Item Open Access Dopaminergic modulation of retinal processing from starlight to sunlight.(Journal of pharmacological sciences, 2019-05-04) Roy, Suva; Field, Greg DNeuromodulators such as dopamine, enable context-dependent plasticity of neural circuit function throughout the central nervous system. For example, in the retina, dopamine tunes visual processing for daylight and nightlight conditions. Specifically, high levels of dopamine release in the retina tune vision for daylight (photopic) conditions, while low levels tune it for nightlight (scotopic) conditions. This review covers the cellular and circuit-level mechanisms within the retina that are altered by dopamine. These mechanisms include changes in gap junction coupling and ionic conductances, both of which are altered by the activation of diverse types of dopamine receptors across diverse types of retinal neurons. We contextualize the modulatory actions of dopamine in terms of alterations and optimizations to visual processing under photopic and scotopic conditions, with particular attention to how they differentially impact distinct cell types. Finally, we discuss how transgenic mice and disease models have shaped our understanding of dopaminergic signaling and its role in visual processing. Cumulatively, this review illustrates some of the diverse and potent mechanisms through which neuromodulation can shape brain function.Item Open Access Genetically Encoded Fluorescent Indicators for Imaging Brain Chemistry.(Biosensors, 2021-04) Bi, Xiaoke; Beck, Connor; Gong, YiyangGenetically encoded fluorescent indicators, combined with optical imaging, enable the detection of physiologically or behaviorally relevant neural activity with high spatiotemporal resolution. Recent developments in protein engineering and screening strategies have improved the dynamic range, kinetics, and spectral properties of genetically encoded fluorescence indicators of brain chemistry. Such indicators have detected neurotransmitter and calcium dynamics with high signal-to-noise ratio at multiple temporal and spatial scales in vitro and in vivo. This review summarizes the current trends in these genetically encoded fluorescent indicators of neurotransmitters and calcium, focusing on their key metrics and in vivo applications.Item Open Access Succinylated octopamine ascarosides and a new pathway of biogenic amine metabolism in Caenorhabditis elegans.(J Biol Chem, 2013-06-28) Artyukhin, Alexander B; Yim, Joshua J; Srinivasan, Jagan; Izrayelit, Yevgeniy; Bose, Neelanjan; von Reuss, Stephan H; Jo, Yeara; Jordan, James M; Baugh, L Ryan; Cheong, Micheong; Sternberg, Paul W; Avery, Leon; Schroeder, Frank CThe ascarosides, small-molecule signals derived from combinatorial assembly of primary metabolism-derived building blocks, play a central role in Caenorhabditis elegans biology and regulate many aspects of development and behavior in this model organism as well as in other nematodes. Using HPLC-MS/MS-based targeted metabolomics, we identified novel ascarosides incorporating a side chain derived from succinylation of the neurotransmitter octopamine. These compounds, named osas#2, osas#9, and osas#10, are produced predominantly by L1 larvae, where they serve as part of a dispersal signal, whereas these ascarosides are largely absent from the metabolomes of other life stages. Investigating the biogenesis of these octopamine-derived ascarosides, we found that succinylation represents a previously unrecognized pathway of biogenic amine metabolism. At physiological concentrations, the neurotransmitters serotonin, dopamine, and octopamine are converted to a large extent into the corresponding succinates, in addition to the previously described acetates. Chemically, bimodal deactivation of biogenic amines via acetylation and succinylation parallels posttranslational modification of proteins via acetylation and succinylation of L-lysine. Our results reveal a small-molecule connection between neurotransmitter signaling and interorganismal regulation of behavior and suggest that ascaroside biosynthesis is based in part on co-option of degradative biochemical pathways.