Central neural circuits involved in the febrile response

描述(由申请人提供)：本提案的目的是深入了解交感神经控制棕色脂肪组织(BAT)的核心机制。交感神经流出到BAT在体温调节中起关键作用，对能量消耗的调节有重要作用。蝙蝠交感神经输出调节的损害或改变与潜在的威胁生命的病理条件和疾病状态有关，如体温过高和肥胖。这项建议的具体目的是确定在发热反应过程中参与调节交感神经流出到蝙蝠的特定中枢神经系统通路。在实验诱导的发热过程中，将对调节交感神经流出到蝙蝠的区域进行抑制，以评估它们参与发热反应。此外，在各种生理和药物操作过程中，将记录单个神经元在发热反应所必需的区域内的活动，以便更好地了解参与发热反应的回路。从这些实验中获得的见解可能最终导致治疗由BAT失调引起的病理情况的新方法。

DESCRIPTION (provided by applicant): The objective of this proposal is to gain insight into the central mechanisms underlying the regulation of sympathetic control of brown adipose tissue (BAT). Sympathetic outflow to BAT plays a critical role in thermoregulation and contributes significantly to the regulation of energy expenditure. Impairments or alterations in the regulation of sympathetic output to BAT are associated with potentially life threatening pathological conditions and disease states such as hyperthermia and obesity. The specific aims of this proposal are to determine the specific central nervous system pathways involved in the regulation of sympathetic outflow to BAT during the febrile response. Inhibition of areas implicated in the regulation of sympathetic outflow to BAT will be performed during experimentally induced fever in order to assess their involvement in the febrile response. In addition, the activity of single neurons within areas found to be necessary for the febrile response will be recorded during various physiological and pharmacological manipulations in order to gain a greater understanding of the circuits involved in febrile thermogenesis. Insights gained from these experiments may eventually lead to novel approaches for treating the pathological conditions resulting from disregulation of BAT.