Optochemical Control of the Neuron-Astrocyte Circuit

星形胶质细胞是大脑和脊髓中的星形胶质细胞。它们是神经系统的结缔组织细胞，将神经细胞与血管联系起来，通过包裹大脑毛细血管，帮助形成血脑屏障。与神经元相比，对星形胶质细胞信号的理解严重滞后，因为星形胶质细胞不具有电生理活性。目前还不知道星形胶质细胞对什么细胞外信号做出反应，以及它们如何对电路功能做出贡献。波斯坎泽提出的这项研究有望阐明这些关键问题。这项研究具有获得新见解和科学知识的巨大潜力。神经回路涉及许多细胞类型，尽管绝大多数回路研究忽略了大脑中的非神经元神经胶质细胞。这项建议解决了我们对神经回路功能中神经胶质细胞的理解上的空白，并利用可光激活工具的力量来解决这些问题。PI应用了一套光化学工具，允许在时空上精确和生理上相关的神经递质释放到大脑皮质回路中的星形胶质细胞和神经元。有望用于研究的化合物将向科学界提供，USCF提供了许多合作机会。PI建议使用Ru-联吡啶(Rubi)笼子通过光激活向星形胶质细胞递送神经递质，并使用第二个激光通过遗传编码的Ca++指示剂监测其分支中的Ca++活动的反应。她将测试星形胶质细胞可以对神经递质做出反应的假设，以及星形胶质细胞是否可以在体内被激活。这项提议研究了星形胶质细胞如何对一系列神经递质做出反应这一非常基本的问题。将开发新的化合物来向细胞传递可控浓度的神经递质。钙反应将被监测，星形胶质细胞的反应将随着浓度的变化而研究。在对脑片进行初步的体外测试之后。她将测试星形胶质细胞可以对神经递质做出反应的假设，以及星形胶质细胞是否可以在小鼠体内被激活。PI与阿根廷的Etchenique实验室有独特的国际合作，并热衷于向生物学学生介绍成像技术，相关的细胞和分子神经科学课程以及伍兹霍尔海洋实验室的职位证明了这一点。本科生将通过USCF暑期研究计划参与，并通过科学和健康教育伙伴关系参与K-12推广活动。

Astrocytes are star-shaped glial cells in the brain and spinal cord. They are connective tissue cells of the nervous system that link nerve cells to blood vessels and, by wrapping round brain capillaries, help to form the blood-brain barrier. Understanding of astrocyte signaling seriously lags in comparison with that of neurons, because the astrocytes are not electrophysiologically active. It is not known what extracellular signals astrocytes respond to and how they contribute to circuit function. The research proposed by Poskanzer has the promise of elucidating these key questions. The research has high potential to gain new insight and scientific knowledge. Neural circuits involve many cell types, although the vast majority of circuit studies neglect to take into account the non-neuronal glial cells in the brain. This proposal addresses gaps in our understanding of glial cells in neural circuit function and harnesses the power of light-activatable tools to tackle them. The PI applies a suite of optochemical tools that allow spatiotemporally precise and physiologically relevant release of neurotransmitter to astrocytes and neurons in cortical brain circuits. Compounds promising for research will be made available to the scientific community, and many collaboration opportunities are available at USCF. The PI proposes to use ruthenium-bipyridine (RuBi) cages to deliver neurotransmitters to astrocytes by photo-activation and monitoring the response from Ca++ activity in their branches by a genetically encoded Ca++ indicator using a second laser. She will test the hypothesis that astrocytes can respond to neurotransmitters and whether astrocytes can be activated in vivo. This proposal investigates the very fundamental question of how astrocytes respond to a range of neurotransmitters. Novel compounds will be developed to deliver controllable concentrations of neurotransmitters to cells. Calcium response will be monitored and astrocyte response will be studied as concentration is varied. Following initial in-vitro testing in brain slices. She will test the hypothesis that astrocytes can respond to neurotransmitters and whether astrocytes can be activated in-vivo in mice.The PI has a unique international collaboration with the Etchenique lab in Argentina and is enthusiastic about introducing biology students to imaging techniques, as evidenced by the relevant Cellular and Molecular Neuroscience course and the position with the Woods Hole Marine Lab. Undergraduate students will be involved through the USCF summer research program, and K-12 outreach through the science and health education partnership.