Collaborative Research: Neuroendocrine Modulation of Circannual Rhythms in Mammals

合作研究：哺乳动物昼夜节律的神经内分泌调节

• 批准号: 1806216
• 负责人: Cory Williams
• 金额: $ 63.74万
• 依托单位: University of Alaska Fairbanks Campus
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-13 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1806216&HistoricalAwards=false
• 关键词: Collaborative; Research; Neuroendocrine; Modulation; Circannual

Predicting how species might alter their annual timing in response to rapid environmental change, including changes in climate, is constrained by insufficient knowledge of the endogenous mechanisms animals use to keep time, the cues used to adjust timing, and the extent to which programmed seasonal cycles are physiologically malleable or plastic. This project investigates the mechanisms that underlie plasticity in the seasonal induction of the neuroendocrine signals that trigger the termination of hibernation and the onset of reproduction in ground squirrels. Unlike most mammals, ground squirrels spontaneously become reproductively competent in constant darkness, without the stimulus of a changing photoperiod. As such, ground squirrels are an ideal organism for studies examining non-photoperiodic control of reproductive timing. Establishing the neuroendocrine mechanisms responsible for transitions between life-history stages will identify target genes for monitoring adaptive genetic responses to environmental change. This investigation integrates research and learning by training graduate students in ecophysiology and neurophysiology, providing opportunities for undergraduates to participate in laboratory experiments. The project also includes outreach to Alaska Native and American Indian high school students and undergraduates for inclusion in research and aims to increase K-12 students' understanding of and engagement in research by participating in Teacher Research Experience programs.In hibernating mammals, a precise integration must occur between the central nervous system signaling cascades controlling thermoregulation through the termination of torpor and the subsequent activation of the reproductive axis; however, the neuroendocrine modulators that regulate these changes and how they are integrated are unknown. In seasonally breeding, photoperiodic vertebrates, the pars tuberalis (PT) of the pituitary plays an essential role in the timing of annual cycles, as it alters hypothalamic thyroid hormone availability by secreting thyroid stimulating hormone in a light- or melatonin-sensitive manner, which acts on neighboring hypothalamic deiodinase expressing cells. The PT thyrotrophs themselves are now considered strong candidates for circannual timer cells, driving a thyroid-dependent seasonal physiology. This research tests the hypothesis that, in the absence of any photic cues, the termination of torpor and onset of reproduction are triggered by spontaneous changes in hypothalamic thyroid status driven by activation of thyrotroph cells in the PT. Additionally, the project tests the hypothesis that plasticity in timing is driven by temperature-induced changes in hypothalamic deiodinase activity and/or through effects on downstream targets of the triiodothyronine signaling pathway that occur independent of the PT.

预测物种可能如何改变其年度的时间，以应对快速的环境变化，包括气候变化，是有限的知识的内源性机制动物用来保持时间，用于调整时间的线索，以及程序化的季节性周期的生理可塑性或塑料的程度不足。本项目研究了地松鼠中触发冬眠终止和生殖开始的神经内分泌信号的季节性诱导的可塑性机制。与大多数哺乳动物不同，地松鼠在持续的黑暗中自发地变得具有繁殖能力，而没有变化的光周期的刺激。因此，地松鼠是研究非光周期控制生殖时间的理想生物体。建立神经内分泌机制，负责生活史阶段之间的过渡将确定目标基因监测适应性遗传反应的环境变化。本研究整合研究与学习，训练研究生在生态生理学和神经生理学，为本科生提供参与实验室实验的机会。该项目还包括对阿拉斯加原住民和美洲印第安人高中生和本科生的外展，以纳入研究，旨在通过参加教师研究经验计划，提高K-12学生对研究的理解和参与度。中枢神经系统通过终止麻痹控制体温调节的信号级联和随后的体温调节之间必须发生精确的整合。生殖轴的激活;然而，调节这些变化的神经内分泌调节剂以及它们如何整合尚不清楚。在季节性繁殖的光周期脊椎动物中，垂体的结节部（PT）在年周期的时间安排中起着至关重要的作用，因为它通过以光敏感或褪黑激素敏感的方式分泌促甲状腺激素来改变下丘脑甲状腺激素的可用性，该促甲状腺激素作用于邻近的下丘脑脱碘酶表达细胞。PT促甲状腺激素细胞本身现在被认为是年周期计时细胞的强有力候选者，驱动甲状腺依赖的季节性生理。本研究测试的假设，即在没有任何光的线索，终止麻痹和繁殖的开始是由自发的变化，下丘脑甲状腺状态的促甲状腺细胞的激活PT驱动。此外，该项目还测试了以下假设：时间可塑性是由温度诱导的下丘脑脱碘酶活性变化和/或通过对三碘甲状腺原氨酸信号通路下游靶点的影响驱动的，这些靶点独立于PT。