Collaborative Research: Targeted neurosteroidogenesis and complex memory function

激素通过血液传播，并对远离其来源的组织产生深远影响。神经元通过突触的微观空间通过电信号和神经递质的释放进行交流。我们最近记录了这两种信号系统的结合，其中一个例子是突触（SES）的雌激素合成。然而，我们对电信号和激素信号如何在突触中相互作用知之甚少，也不知道这种SES如何影响记忆功能等复杂行为。我们也不知道学习是否会影响SES。我们将使用具有丰富SES的斑胸草雀来了解突触类固醇合成如何与膜电活动和神经递质释放相互作用。然后，我们将探讨SES如何调节新学习空间信息的学习、存储和回忆。最后，我们将探讨与学习、记忆和社会地位相关的基因组变化。该项目的研究人员都致力于本科教育，并将研究机会扩展到学生和地区高中教师，从而增加了在当地机构的推广。PI将主持一个流媒体视频节目，突出健康食品准备和荷尔蒙变化之间的相互作用。最后，我们将提供关于LBGT+合唱团生理和声乐变化的内容，以及关于激素治疗对声乐表演的影响。这些外展活动旨在利用研究人员的学术、外展和公众参与来提高不同公民对科学研究的认识。突触的类固醇合成证明突触分泌信号可能是一个结合旁分泌和电信号的信号系统。雀脑中丰富的突触芳香酶使其成为理解电活动和类固醇供应之间相互作用的宝贵模型。此外，鸟类海马（HP）的可及性、丰富的突触芳香化酶及其在空间记忆中的既定作用，为理解突触芳香化在记忆形成和表现中的作用提供了前所未有的机会。我们建议使用生化、行为和基因组技术来了解离子通量如何影响突触中的激素合成和神经递质释放，HP中的芳香化如何影响记忆功能的组成部分，以及海马转录组的变化如何被芳香化和学习改变。该提案结合了两所主要本科院校的研究人员的技能，他们都致力于学术和公共教育。pi将欢迎高中教师和本科生到他们的实验室进行暑期实习，并将为神经科学专业的本科生设计和实施一门新的神经解剖学课程。公众宣传将包括一个流媒体烹饪节目，讨论健康食品制备的内分泌学和生理学后果。最后，PI和一位音乐方面的同事将为LBGT+社区的合唱表演者设计并提供有关慢性激素治疗期间呼吸和声音变化的内容。这些外展活动将使不同年龄、性别、种族和社会经济群体的广泛公众受益。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Hormones travel through the blood and profoundly affect tissues far from their source. Neurons communicate with electrical signals and the release of neurotransmitters across the microscopic space of a synapse. We have recently documented a combination of these two signaling systems, one example of which is estrogen synthesis at the synapse (SES). However, we know little about how electrical and hormonal signaling interact at the synapse, or how this SES may affect complex behaviors like memory function. Neither do we know if learning affects SES. We will use the zebra finch, a species with abundant SES to understand how synaptic steroid synthesis interacts with membrane electrical activity and neurotransmitter release. Then, we will ask how SES modulates learning, storage and recall of newly learned spatial information. Lastly, we will probe changes in the genome associated with learning, memory, and SES. The investigators on this project are all committed to undergraduate education and extend research opportunities to students and area high school teachers, thereby increasing outreach at local institutions. The PI will host a streaming video show highlighting the interactions between healthy food preparation and hormonal change. Finally, we will provide content on the physiological and vocal changes to LBGT+ choruses and choirs on the effects of hormone therapy on vocal performance. These outreach activities are designed to exploit the researchers’ scholarly, outreach, and public engagement to increase the awareness of scientific research to a diverse set of citizens. Synaptocrine signaling, evidenced by steroid synthesis at the synapse may be a signaling system that combines paracrine and electrical signaling. The abundant synaptic aromatase in the finch brain makes it an invaluable model in understanding the interplay between electrical activity and steroid provision. Further, the accessibility of the avian hippocampus (HP), the plentiful synaptic aromatase therein, and its established role in spatial memory, allow for an unparalleled opportunity to understand the role of synaptocrine aromatization in memory formation and performance. We propose to use biochemical, behavioral, and genomic techniques to understand how: ionic flux affects hormone synthesis and neurotransmitter release at the synapse, how aromatization in the HP affects components of memory function, and how changes in the hippocampal transcriptome are altered by aromatization and learning. This proposal combines the skills of researchers at two predominantly undergraduate institutions, all of whom are committed to academic and public education. The PIs will welcome high school teachers and undergraduates into their laboratories for summer internships and will design and implement a new course in Neuroanatomy for undergraduates in Neuroscience. Public outreach will consist of a streaming cooking show that discusses the endocrinology and physiological consequences of healthy food preparation. Finally, the PI and a colleague in Music will design and provide content to choral performers in the LBGT+ community on respiratory and vocal changes during chronic hormone-therapy. Taken together these outreach activities will benefit a wide array of the public across ages, genders, ethnicities, and socioeconomic groups.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.