Nitric oxide-dependent synaptic plasticity in the retina

这个项目解决了一氧化氮在中枢神经系统神经元通讯中产生灵活性的作用。 一氧化氮是一氧化氮合酶响应神经元活动而产生的气体信号分子。 神经元之间的通信发生在突触处，并且神经元和神经元回路的活动取决于兴奋性和抑制性突触相互作用的平衡。 抑制作用依赖于神经元细胞质中的氯离子浓度，并且已经证明一氧化氮增加细胞质中的氯离子浓度。 增加胞质氯具有减少抑制或将其转化为兴奋的作用。 因此，一氧化氮可以将抑制转换为兴奋，并改变神经元回路的活动。该项目将确定内部氯化物的来源，可以通过一氧化氮释放和参与释放的机制。该项目的目标将通过电生理学和分子生物学的结合来实现。这项工作是我们理解神经系统功能的基础，因为一氧化氮对胞质氯化物的控制是一种以前未发现的机制，它显著增加了正常抑制性突触的灵活性。此外，该项目还探索了视网膜神经元中内部氯化物的一氧化氮释放，但这种氯化物释放也在大脑其他地方的神经元中得到了证实。 因此，这些结果将对中枢神经系统多个区域的突触功能调节产生重要影响。 更广泛的影响包括研究生和本科生在PI实验室的参与。 PI将参加路易斯安那州科学学院生物医学研究网络夏季研究计划和路易斯安那州立大学霍华德休斯医学研究所本科夏季研究计划。 在这些项目中，PI将招募代表性不足的少数民族和妇女。此外，PI是路易斯安那州数学和科学教师协会的导师，该协会为当地公立学校教师提供额外的科学教育。

This project addresses the role of nitric oxide in generating flexibility in neuronal communication in the central nervous system. Nitric oxide is a gaseous signaling molecule that is generated by the enzyme nitric oxide synthase in response to neuronal activity. Communication between neurons occurs at synapses and the activity of neurons and neuronal circuits are dependent upon the balance of excitatory and inhibitory synaptic interactions. Inhibition is dependent upon the concentration of chloride in the neuronal cytoplasm and it has been demonstrated that nitric oxide increases chloride concentration in the cytoplasm. Increasing cytosolic chloride has the effect of either reducing inhibition or converting it into excitation. Hence, nitric oxide can switch inhibition to excitation and alter the activity of neuronal circuits. This project will determine the sources of internal chloride that can be released by nitric oxide and the mechanisms involved in the release. The goals of the project will be achieved using a combination of electrophysiology and molecular biology. This work is fundamental to our understanding of nervous system function because control of cytosolic chloride by nitric oxide is a previously undiscovered mechanism that dramatically increases the flexibility of normally inhibitory synapses. Furthermore, the project explores the nitric oxide release of internal chloride in a retinal neuron but this chloride release has also been demonstrated in neurons from elsewhere in the brain. As such, these results will have important ramifications for regulation of synaptic function in multiple regions of the central nervous system. The broader impacts include participation by graduate students and undergraduates in the PI's laboratory. The PI will participate in the College of Science Louisiana Biomedical Research Network Summer Research Program, and the LSU Howard Hughes Medical Institute Undergraduate Summer Research Program. In these programs, the PI will recruit underrepresented minorities and women. In addition, the PI is a mentor at the Louisiana Math and Science Teacher Institute, which provides additional science education for local public school teachers.