CAREER: Chemical Tools for Bio-Orthogonal Neuromodulation

在化学系生命过程化学项目的支持下，雪城大学（Syracuse University）的雷切尔·斯坦哈特（Rachel Steinhardt）将开发化学工具，以了解单个细胞如何交流以产生大脑活动。破译这种交流有望使我们对学习、情绪和睡眠等现象有新的认识。重点研究了探针的化学合成及其化学生化性能的优化。然后将对它们进行测试，以确定探针以空间或时间定义的方式与目标相互作用的能力，然后将其与生化或神经元事件相关联。该课程的跨学科性质将使研究生和本科生获得现代研究技术方面的专业知识。该项目还整合了一个拓展项目，在雪城市学区中学的课后项目中教授化学。神经科学中最令人困惑的挑战之一是如何解释大脑的学习和改变自身的能力，在使用固定的解剖学连接的情况下创造看似无限的行为和状态（睡眠，清醒，注意力）。为了回答这些问题，有必要确定膜结合受体结合事件与神经元集合活动之间的联系。不幸的是，缺乏通过刺激天然受体来充分探测神经活动的化学工具。Steinhardt实验室将通过合成用于空间定义的天然受体控制和时间定义的神经化学信号的探针来解决这一需求，然后将其用于生化和基于原代细胞的分析。这些探针是研究人员用光控制天然化学突触的小分子方法。这种探针有望促进自下而上的实验（即细胞到神经网络），以确定学习与神经状态灵活性以及天然多巴胺和血清素受体亚型调节之间的机制关系。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。

With the support of the Chemistry of Life Processes Program in the Division of Chemistry, Rachel Steinhardt of Syracuse University will develop chemical tools to understand how individual cells communicate to create brain activity. Decoding this communication promises to enable new insights into phenomena such as learning, mood, and sleep. The research focuses on the chemical synthesis of probes and optimization of their chemical and biochemical properties. They will then be tested in assays that determine the ability of the probe to interact with a target in a spatially- or temporally defined manner, which can then be correlated to a biochemical or neuronal event. The interdisciplinary nature of this program will allow graduate students and undergraduates to gain expertise in modern research techniques. The project also integrates an outreach program to teach chemistry in an after school program at middle schools Syracuse City School District.One of the most perplexing challenges in neuroscience is how to explain the brain’s ability to learn and change itself, creating seemingly infinite behaviors and states (sleeping, wakefulness, attention) while using a fixed anatomical connectivity. To answer these questions, it is necessary to define the link between membrane-bound receptor binding events and the ensemble activity of neurons. Unfortunately, there is a paucity of chemical tools to adequately probe neural activity via stimulation of the native receptors. The Steinhardt lab will address this need by synthesizing probes for spatially defined native receptor control and temporally defined neurochemical signaling,that will then be used in biochemical and primary cell-based assays. These probes are small molecule methods for researchers to control native chemical synapses with light. Such probes are expected to facilitate bottom-up experiments (i.e., cell to neural network) to determine the mechanistic relationship between learning and neural state flexibility and modulation of native dopamine and serotonin receptor subtypes.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.