<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Characterization of mouse preoptic area cellular populations\r\ninvolved in thermoregulation"^^ . "Thermoregulation is a dynamic homeostatic process, tightly regulated by the autonomic nervous \r\nsystem. How the brain coordinates maintenance of the body temperature within a narrow range of 37˚C, \r\na condition that is needed for the survival of most of the species, remains unclear. Among the brain regions \r\nimplicated in thermoregulation is the anterior portion of the hypothalamus, the preoptic area (POA). In \r\nthis region neurons that respond to direct temperature stimuli and to the skin and spinal cord warming \r\nwere found, suggesting that these warm-sensitive neurons (WSNs), are the cells that detect deep brain \r\ntemperature and integrate it with temperature information from the periphery. The limiting factor in \r\nstudying the WSNs of the POA and their role in thermoregulation is the lack of specific molecular markers \r\nthat identify them. \r\nTherefore, the goal of this thesis work was to characterize WSNs of the POA at the molecular level \r\nand to find their genetic marker(s). To achieve this goal I used a primary POA cell culture and performed \r\ncalcium imaging while applying a temperature stimulus of 45˚C in the presence and the absence of the \r\nTRPM2 antagonist, 2-Aminoethoxydiphenyl borate (2-APB). I identified and hand-picked temperature \r\nresponding cells and temperature non-responding cells for the single-cell RNA-sequencing (scRNA-seq). \r\nAnalysis of the scRNA-seq data pointed to the limitations of the P9 cell culture used. The majority of the \r\ntemperature non-responding cells expressed glial marker genes together with neuronal markers, a \r\ncombination not found in vivo. I concluded that the genetic heterogeneity of the sequenced cells was too \r\nlarge and putative WSNs’ molecular markers identified from cultured neurons would be ambiguous. In \r\naddition, to find markers of WNSs one has to take another approach, such as Patch-seq to analyze these \r\nneurons in more natural conditions.\r\nOne of the POA neuronal populations activated by a change in ambient temperature is expressing \r\nleptin receptor (POALepR). These neurons also exhibit an increase in action potential firing frequency (AP \r\nFF) during the process of chronic heat exposure to 36˚C that also leads to an increased heat endurance (at \r\n39˚C). in mice. This intrinsic property of neurons (not affected by synaptic blockers), seems to be needed \r\nfor a mouse to endure heat, as the animals in which the firing of POALepR is abolished fail to do so. \r\nTo learn more about the role of the POALepR neurons in the heat acclimation process I used FACS \r\n(Fluorescence Activated Cell Sorting) to isolate the POALepR neurons from POA of non-acclimated and \r\nacclimated ( 5 and 30 days at 36 ˚C) LeprCreHTB mice and performed RNA sequencing. I identified three \r\ngenes Kcnq2, Kcnn2, and Kcnh2, all three coding for potassium ion channels, whose expression level \r\nchanged with the course of heat acclimation. I have tested the functionality of these ion channels in AP \r\nviii\r\nfiring of the POALepR neurons, by employing electrophysiology and pharmacology in acute POA slices. Ion \r\nchannels Kv7.2 and Kv11.1, coded by Kcnq2, and Kcnh2, respectively, exhibited a role in shaping the AP \r\nfiring of POALepR neurons. Applying the antagonist of Kv7.2 disrupted harmonious AP firing of POALepR\r\nneurons coming from acclimated mice, rendering their membrane potential unsteady and their firing \r\nbursty. In addition, the application of the Kv11.1 antagonist increased the AP FF of POALepR neurons even \r\nfurther in the long-term acclimated condition. \r\nHeat acclimation is a naturally occurring process happening across mammalian species, including \r\nhumans. It is important for enduring physical burdens in hotter climates as it leads to the improved \r\nfunction of the thermoregulatory system. It is forthright to hypothesize that the POA, the central regulator \r\nof temperature homeostasis, plays a role in heat acclimation. However, knowledge about it is scarce. \r\nKnowing which molecules change in POALepR neurons transcriptome to increase firing, and to which other \r\nthermoregulatory relays these neurons project will help us understand their role and the role of POA in \r\nheat acclimation."^^ . "2023" . . . . . . . "Kristina"^^ . "Zuza"^^ . "Kristina Zuza"^^ . . . . . . "Characterization of mouse preoptic area cellular populations\r\ninvolved in thermoregulation (PDF)"^^ . . . "Doctoral_Thesis_Kristina_Zuza.pdf"^^ . . . "Characterization of mouse preoptic area cellular populations\r\ninvolved in thermoregulation (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Characterization of mouse preoptic area cellular populations\r\ninvolved in thermoregulation (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Characterization of mouse preoptic area cellular populations\r\ninvolved in thermoregulation (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Characterization of mouse preoptic area cellular populations\r\ninvolved in thermoregulation (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Characterization of mouse preoptic area cellular populations\r\ninvolved in thermoregulation (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #32305 \n\nCharacterization of mouse preoptic area cellular populations \ninvolved in thermoregulation\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .