Collaborative Research: Targeted neurosteroidogenesis and complex memory function

荷尔蒙通过血液传播，对远离其来源的组织产生深远的影响。神经元通过电信号进行交流，并通过突触的微观空间释放神经递质。我们最近记录了这两个信号系统的组合，其中一个例子是突触处雌激素的合成(SES)。然而，我们对电和荷尔蒙信号如何在突触上相互作用，或者这种SES如何影响记忆功能等复杂行为知之甚少。我们也不知道学习是否会影响SES。我们将使用斑马雀，一种拥有丰富的SES的物种来了解突触类固醇合成是如何与膜电活动和神经递质释放相互作用的。然后，我们将询问SES如何调节对新学习的空间信息的学习、存储和回忆。最后，我们将探索与学习、记忆和SES相关的基因组变化。该项目的研究人员都致力于本科教育，并将研究机会扩大到学生和地区高中教师，从而增加了在当地机构的覆盖面。PI将主持一个流媒体视频节目，强调健康食品准备和荷尔蒙变化之间的互动。最后，我们将提供有关LBGT+合唱团的生理和发声变化的内容，以及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，提高不同公民对科学研究的认识。突触激素合成所证实的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。雀类脑中丰富的突触芳香酶使其成为了解电活动和类固醇供应之间相互作用的宝贵模型。此外，鸟类海马体(HP)的可及性、其中丰富的突触芳香化酶及其在空间记忆中的既定作用，为理解突触分泌芳构化在记忆形成和表现中的作用提供了一个无与伦比的机会。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，以及海马区转录组的变化如何通过芳构化和学习来改变。这项建议结合了两个以本科生为主的机构的研究人员的技能，这两个机构都致力于学术和公共教育。PIS将欢迎高中教师和本科生进入他们的实验室进行暑期实习，并将为神经科学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，讨论健康食品准备的内分泌学和生理后果。最后，PI和一位音乐方面的同事将设计并向LBGT+社区的合唱表演者提供关于慢性激素治疗期间呼吸和声音变化的内容。综上所述，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。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.