Activity-Dependent Regulation of Early Stages in Synapse Formation

劳拉·N Borodinsky提案#0516871突触形成早期阶段的活动依赖性调节神经系统功能依赖于称为突触的适当连接的建立。该项目的假设是，突触形成的早期事件是由电活动塑造的。电活动的改变改变遵循稳态范例的神经递质表达（Borodinsky等人，2004年）。这一发现引出了一个问题，即神经递质表达的改变是否会导致脊髓轴突的改道。不同类型神经元的轴突寻路模式将在活动受到干扰后进行。实验还将解决神经活动影响突触后细胞中表达的神经递质受体类别的假设。该项目的最终目标将是测试这样一种假设，即当活动被操纵时，神经元和靶细胞之间可以形成新的突触，即不同递质的表达将与相应受体的表达相匹配。该项目对发育神经科学领域非常重要，因为它挑战了神经系统发育的早期事件完全由预定的遗传程序控制的观点，而不依赖于电活动。这项研究中获得的信息可能对我们如何看待神经系统发育中的障碍和相关病理具有重要意义。调节靶细胞中分泌特定递质和递质敏感性的神经元数量的能力具有巨大的社会效益，为神经系统疾病提供潜在的治疗方法，NSF对本提案的支持将是作为一个代表性不足的群体的独立科学家的进步至关重要。 这笔赠款将允许继续培训学生，并将允许主要研究员发展作为监督员的技能。NSF的支持将确保在科学期刊上发表结果，并参加科学会议，以传播本提案的结果，并提高对神经系统发育的理解。

Laura N. Borodinsky Proposal # 0516871Activity-dependent regulation of early stages in synapse formationNervous system function relies on the establishment of appropriate connections, called synapses. The hypothesis of the proposed project is that early events in synapse formation are shaped by electrical activity. Alterations in electrical activity modify neurotransmitter expression following a homeostatic paradigm (Borodinsky et al., 2004). This finding leads to the question whether altered neurotransmitter expression causes rerouting of axons in the spinal cord. Axonal pathfinding patterns for different neuronal types will be followed after activity has been perturbed. The experiments will also address the hypothesis that neural activity influences the classes of neurotransmitter receptors expressed in postsynaptic cells. The ultimate goal of the project will be to test the hypothesis that novel synapses between neurons and target cells can be formed when activity is manipulated, i.e. that expression of different transmitters will be matched by the expression of corresponding receptors. The proposed project is important for the field of developmental neuroscience because it challenges the view that early events in nervous system development are governed entirely by a predetermined genetic program, independent of electrical activity.The information gained in this study could have significant implications for how we think about disorders in developmental wiring of the nervous system and related pathologies. The ability to regulate the number of neurons secreting particular transmitters and transmitter sensitivity in target cells has the power to be of substantial societal benefit, providing potential therapies for neurological disorders.Support from NSF for the present proposal will be crucial in the advancement as an independent scientist of a member of an underrepresented group. This grant will allow continued training of students, and will allow the principal investigator to develop skills as a supervisor. NSF support will ensure publication of results in scientific journals, and participation in scientific meetings to disseminate the results from this proposal and enhance understanding of nervous system development.