Systems NeuroscienceResearch PaperDifferent populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regions
Section snippets
Animals
All experimental animal protocols were reviewed and approved by Animal Care and Use Committee of Oregon Health and Science University and conform to the National Institutes of Health Guide for the Care and Use of Laboratory Animals. All efforts were made to minimize the number of animals used and their suffering. Male Sprague-Dawley rats (200–250 g, Charles River, Indianapolis, IN, USA) were housed two per cage with ad libitum access to feed and water in a room air-conditioned at 24±2 °C with a
Results
Following injections of CTbs conjugated with different fluorophores into the DMH and the rRPa (Fig. 1), many neuronal cell bodies in the POA were retrogradely labeled with CTb (Fig. 2, Fig. 3). Neurons labeled with cholera toxin b-subunit derived from the dorsomedial hypothalamus (DMH-CTb) and those labeled with cholera toxin b-subunit derived from the rostral raphe pallidus nucleus (rRPa-CTb) showed similar distributions in the MnPO and MPO, both of which overlapped EP3R-immunoreactive regions
Discussion
The major finding in the present study is that although the DMH and the rRPa receive projections from many POA neurons that express prostaglandin EP3Rs, only a very small number of EP3R-expressing POA neurons project to both the DMH and the rRPa. In light of the critical role of EP3Rs in POA neurons as a sensor of the pyrogenic mediator, PGE2 (Lazarus et al., 2007), the present result indicates that fever signaling to the DMH and to the rRPa from the POA is mediated by separate populations of
Conclusion
In conclusion, the results from the present anatomical study using a molecular marker for pyrogen-receptive neurons indicate that separate sets of projection neurons mediate pyrogenic signaling from the POA to neurons in two different caudal brain sites: the DMH and the rRPa. These separate outflow pathways from the POA potentially mediate differential inhibitory control of the sympathoexcitatory drive determining BAT thermogenesis and cutaneous vasoconstriction during fever development, and
Acknowledgments
This work was supported by National Institutes of Health (NIH) grants NS40987 and DK57838 to S.F.M. K.N. was a fellow for research abroad supported by the Japan Society for the Promotion of Science. Acquisition of confocal images was supported by NIH instrumentation grant RR016858.
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2022, Brain, Behavior, and ImmunityCitation Excerpt :POA neurons contribute to the COX-2/PGE2-mediated activation (or disinhibition) of neurons residing in the DMH (da Conceicao et al., 2020) and rRPa (Machado et al., 2020). Activity of excitatory amino acid receptors within the DMH is required for BAT thermogenesis but not for cutaneous vasoconstriction, while activation of those receptors within the rRPa is required for both BAT thermogenesis and cutaneous vasoconstriction in response to administration of PGE2 in the POA (Madden and Morrison 2003, Madden and Morrison 2004, Rathner et al., 2008, Nakamura et al. 2009, McAllen and McKinley 2018). In contrast to the well described neural pathway(s) responsible for COX-2/PGE2-dependent fever, the pathway(s) mediating COX-independent components of fever are not known.
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2019, REACHCitation Excerpt :The dorsomedial hypothalamic nucleus has been proposed to receive inputs from the preoptic area. The preoptic area is a center of integrating centrally and peripherally thermal signals, and sending the outputs to the rostral raphe pallidus in the medulla, the area containing premotor neurons that innervate SNS to BAT [1193,897,891]. Microinjections of either a NMDAR agonist or a non-NMDAR agonist into the rostral raphe pallidus of rats produced an increased SNS-outflow to the BAT following an upregulated thermogenesis and disinhibition of dorsomedial hypothalamic nucleus neurons [185].