Collaborative Research: Targeted neurosteroidogenesis and complex memory function

合作研究：靶向神经类固醇生成和复杂记忆功能

• 批准号: 2050260
• 负责人: Colin Saldanha
• 金额: $ 108.86万
• 依托单位: American University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2050260&HistoricalAwards=false
• 关键词: Collaborative; Research; Targeted; neurosteroidogenesis; complex

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.

激素通过血液传播，并深刻地影响远离其来源的组织。神经元通过突触的微观空间与电信号和神经递质的释放进行通信。我们最近记录了这两个信号系统的组合，其中一个例子是雌激素在突触合成（SES）。然而，我们对电信号和激素信号如何在突触处相互作用，或者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。我们将使用斑胸草雀，一种具有丰富SES的物种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，我们将询问SES如何调节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。该项目的调查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将举办一个流媒体视频节目，突出健康食物准备和荷尔蒙变化之间的相互作用。最后，我们将提供有关LBGT+合唱团和合唱团的生理和声乐变化的内容，以及激素治疗对声乐表演的影响。这些推广活动旨在利用研究人员的学术，推广和公众参与，以提高科学研究的意识，以不同的公民。突触内分泌信号，通过在突触处的类固醇合成证明，可能是结合旁分泌和电信号的信号系统。雀脑中丰富的突触芳香化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（HP）的可访问性，丰富的突触芳香化酶，其在空间记忆中的既定作用，允许一个无与伦比的机会来了解突触分泌芳香化在记忆形成和表现中的作用。我们建议使用生物化学，行为和基因组技术来了解如何：离子通量影响激素合成和神经递质在突触释放，如何芳构化的HP影响记忆功能的组成部分，以及如何在海马转录组的变化被改变芳构化和学习。该提案结合了两个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，并将为神经科学本科生设计和实施一门新的神经解剖学课程。公共宣传将包括一个流式烹饪节目，讨论健康食品制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为LBGT+社区的合唱表演者设计和提供关于慢性呼吸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NSF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。

项目成果

Glial synthesis of estrogen following injury.

损伤后胶质细胞合成雌激素。

• 发表时间: 2021
• 期刊: Current opinion in endocrine and metabolic research
• 作者: Colin J. Saldanha

A Transcriptomic Pipeline Adapted for Genomic Sequence Discovery of Germline-Restricted Sequence in Zebra Finch, Taeniopygia guttata.

• DOI: 10.1093/gbe/evab088
• 发表时间: 2021-06-08
• 期刊: Genome biology and evolution
• 影响因子: 3.3
• 作者: Asalone KC;Takkar AK;Saldanha CJ;Bracht JR
• 通讯作者: Bracht JR

Sex Hormones and Glutamatergic Neurotransmission: A review of the literature.

性激素和谷氨酸神经传递：文献综述。

• 发表时间: 2023
• 期刊: Journal of neuroendocrinology
• 影响因子: 3.2
• 作者: Goyette, MJ;Murray, S;Saldanha, CJ &
• 通讯作者: Saldanha, CJ &