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，并深刻影响远离其来源的神经元，并通过突触的微观空间释放神经递质，其中一个例子是雌激素。然而，我们对突触处的电信号和激素信号如何相互作用，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。斑胸草雀是一种具有丰富 SES 的物种，旨在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。该项目的研究人员都致力于本科教育，并为学生和地区高中教师提供研究机会，从而扩大在当地机构的推广范围。之间的相互作用最后，我们将为 LBGT+ 合唱团和合唱团提供有关激素治疗对声乐表现影响的内容。这些外展活动旨在利用研究人员的学术、外展和公众影响。突触分泌信号传导可能是一种结合了旁分泌和电信号传导的信号系统，以提高不同公民对科学研究的认识。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，鸟类海马体（HP）的可及性、其中丰富的突触芳香酶及其在空间记忆中的既定作用，为理解鸟类海马体（HP）提供了无与伦比的机会。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 的芳香化影响记忆功能的组成部分，以及芳香化和学习如何改变海马转录组的变化。该提案结合了两个主要本科机构的研究人员的技能，所有这些研究人员都致力于学术和公共教育。高中教师和本科生进入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，其中包括一个流媒体烹饪节目，讨论健康的内分泌学和生理后果。最后，PI 和一位音乐同事将为 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。这些外展活动将使各年龄段的广大公众受益。 、性别、种族和社会经济群体。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点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

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 &

Spatial and temporal specificity of neuroestradiol provision in the songbird

• DOI: 10.1111/jne.13192
• 发表时间: 2022-08-19
• 期刊: JOURNAL OF NEUROENDOCRINOLOGY
• 影响因子: 3.2
• 作者: Saldanha，Colin J.

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