Collaborative Research: Neuroendocrine Modulation of Circannual Rhythms in Mammals

由于缺乏对动物保持时间的内源性机制、用于调整时间的线索以及程序化的季节周期在多大程度上具有生理可塑性或可塑性的知识，预测物种如何改变它们的年度时间以应对快速的环境变化，包括气候变化，受到了限制。本项目研究了在触发地松鼠结束冬眠和开始繁殖的神经内分泌信号的季节性诱导中可塑性的机制。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繁殖时间的理想生物。建立负责生活史阶段之间过渡的神经内分泌机制将确定监测环境变化的适应性遗传反应的靶基因。本研究通过培养生态生理学和神经生理学的研究生，将研究与学习结合起来，为本科生提供参与实验室实验的机会。该项目还包括向阿拉斯加原住民和美国印第安人高中生和本科生推广，以将其纳入研究，并旨在通过参加教师研究体验项目来提高K-12学生对研究的理解和参与。在冬眠的哺乳动物中，中枢神经系统信号级联通过终止冬眠控制体温调节和随后的生殖轴激活之间必须发生精确的整合；然而，调节这些变化的神经内分泌调节剂以及它们是如何整合的尚不清楚。在季节性繁殖的光周期脊椎动物中，垂体结节部（PT）在年度周期的时间上起着至关重要的作用，因为它通过以光或褪黑激素敏感的方式分泌促甲状腺激素，从而改变下丘脑甲状腺激素的可用性，这种激素作用于邻近的下丘脑脱碘酶表达细胞。PT促甲状腺细胞本身现在被认为是周期性定时细胞的有力候选者，驱动甲状腺依赖的季节性生理。本研究验证了在没有任何光线索的情况下，下丘脑甲状腺状态的自发变化是由PT中甲状腺营养细胞的激活所驱动的，从而触发了冬眠的终止和繁殖的开始。该项目验证了一个假设，即时间的可塑性是由温度引起的下丘脑去碘酶活性的变化和/或通过对独立于PT发生的三碘甲状腺原氨酸信号通路下游目标的影响驱动的。

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.