RUI: Neural Basis of Pubertal Shifts in Stress Reactivity

青春期是一个重要的发育阶段，以生理和神经功能的转变为标志。虽然大多数人都很欣赏这一时期荷尔蒙的变化，但青少年经历的类型也发生了巨大的变化。这些经历会导致环境中压力源的暴露增加。越来越多的研究表明，在这一阶段，个体对压力的反应发生了重大变化，但我们对这些变化背后的生物学机制知之甚少。解决我们在理解上的这些差距是很重要的，因为压力会破坏身体和大脑系统，这些系统在这段时间里正在发育成成年人的模式。利用神经解剖学和生物化学研究相结合的实验动物模型，这些实验将开始揭示介导青春期应激反应变化的神经机制。这些研究的结果将扩展我们对青春期和压力如何相互作用影响大脑和身体的理解。重要的是，这些研究将在巴纳德学院进行，这是一所全女子文理学院。因此，除了导致我们对神经发育的理解取得进展外，支持这一提议将为许多女性本科生提供参与实验研究各个方面的教育机会。下丘脑室旁核（PVN）在整合来自协调应激反应的大脑区域的信息方面起着关键作用。与成年动物相比，在青春期前的PVN中发现了更高水平的神经激活，以应对压力，这导致了PVN连接和/或功能的发育变化有助于青春期应激反应的改变的假设。该项目将通过评估青春期在连接、表现型和投射到PVN的大脑区域的激活方面的差异来验证这一假设。具体来说，神经束示踪结合兴奋性或抑制性神经元的免疫组织化学标记物将用于青春期前和成年应激大鼠。该项目还将通过评估受体表达和测量激素水平来检测青春期前和成年暴露于压力下的大鼠PVN中兴奋性或抑制性受体调节剂的定向递送后，PVN中兴奋性和抑制性信号的变化。这些研究将探讨应激反应在青春期转变的神经机制，并提供青少年和成人神经系统如何处理应激刺激的差异信息。

Puberty is a significant stage of development marked by transitions in both physiological and neural function. Though most people appreciate the hormonal changes that occur during this period, the types of experiences that an adolescent encounters also change dramatically. These experiences can result in increased exposure to stressors in the environment. A growing body of research indicates that how an individual responds to stress changes substantially during this stage, but we know little about the biological mechanisms that underlie these shifts. It is important to address these gaps in our understanding, because stress can disrupt body and brain systems that are developing into their adult-like patterns during this time. Using an experimental animal model that combines studies at the neuroanatomcial and biochemical levels, these experiments will begin to reveal the neural mechanisms that mediate the pubertal changes in stress responsiveness. The results of these studies will extend our understanding of how puberty and stress interact to affect both the brain and body. Importantly, these studies will be undertaken at Barnard College, an all women's liberal arts college. Thus, in addition to leading to advances in our understanding of neurodevelopment, support of this proposal will provide many female undergraduates with educational opportunities to take part in all aspects of experimental research.The paraventricular nucleus of the hypothalamus (PVN) plays a pivotal role in integrating information from brain areas that coordinate the stress response. Greater levels of neural activation have been found in the PVN of prepubertal compared to adult animals in response to stress, leading to the hypothesis that developmental changes in the connectivity and/or function of the PVN contribute to pubertal alterations in stress reactivity. This project will test this hypothesis by assessing pubertal differences in the connectivity, phenotype, and activation of brain areas that project to the PVN. Specifically, neural tract tracing combined with immunohistochemical markers of excitatory or inhibitory neurons will be used in prepubertal and adult rats exposed to stress. This project will also examine pubertal changes in excitatory and inhibitory signaling in the PVN by assessing receptor expression and measuring hormone levels following site-directed delivery of excitatory or inhibitory receptor modulators in the PVN of prepubertal and adult rats exposed to stress. These studies will probe neural mechanisms responsible for the pubertal transitions in stress reactivity, and provide information on how the adolescent and adult nervous systems differentially process stressful stimuli.