Spike-triggered current source-density analysis: The synaptic impact of a single

尖峰触发电流源密度分析：单个电流的突触影响

• 批准号: 7611411
• 负责人: HARVEY A SWADLOW
• 金额: $ 22.89万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7611411
• 关键词: Abbreviations; Area; Axon; Beds; Behavior Disorders; Brain; Caliber; Cell Communication; Cells; Characteristics; Collaborations; Communication; Communities; Complex; Contralateral; Data; Development; Disease; Distant; Electric Stimulation; Electrodes; Elements; Environment; Event; Felis catus; Figs - dietary; Future; Goals; Human; Image; In Vitro; Interneurons; Knowledge; Label; Lateral Geniculate Body; Measures; Mental Health; Methods; Modeling; Monitor; Morphology; Neurons; Oryctolagus cuniculus; Penetration; Physiologic pulse; Population; Psyche structure; Running; Slice; Somatosensory Cortex; Source; Synapses; System; Testing; Thalamic structure; Time; Training; Visual Cortex; Work; awake; base; biocytin; density; extracellular; hippocampal pyramidal neuron; in vivo; interest; postsynaptic; presynaptic; professor; relating to nervous system; response; tool

DESCRIPTION (provided by applicant): The hallmark of neuronal systems lies in the vast, modifiable functional interconnections among the elements. Understanding brain function requires a detailed knowledge of how such functional connectivity is achieved, but the tools for analysis of synaptic communication in the waking brain are very limited. In vitro, cell-to-cell connectivity has been studied using paired intracellular recordings or minimal electrical stimulation of thalamic or other afferents. These methods have yielded a wealth of information about cell-to-cell interactions, but in vitro slices eliminate many of the synaptic and modulatory inputs that operate in intact brains. Moreover, these methods are difficult to apply in vivo, where the primary tool for examining synaptic interactions has been extracellular cross-correlation. The above in vitro tools, as well as in vivo extracellular cross-correlation, generally yield an analysis of the synaptic impact of a single presynaptic neuron on a single (or on a very few) postsynaptic target cells. However, some experimental questions require a view of the overall, global synaptic impact generated by a single presynaptic neuron on its targeted cortical domain. We have been developing a method that yields such a view, referred to as spike-triggered current source-density analysis. This method allows an analysis of the synaptic impact generated by a single presynaptic neuron on a neuronal population contained within a restricted cortical cylinder of ~200 microns diameter. This method has proved very useful in the study of systems in which the presynaptic neuron generates a relatively powerful and focal impact on the targeted domain. The goal of the proposed work is to gain a better understanding of both the strengths and limitations of this method, and to extend its use to weaker and less focal neuronal connections, which are more prevalent in the brain. By doing so, the proposed work will provide the scientific community with a new and powerful tool for the study of functional connectivity in the intact, awake brain. The current work will have an important impact on our ability to monitor functional neuronal connectivity in intact, awake brains. A disruption in neural communication has been associated with a wide range of mental diseases. This proposal involves development of new methods to study communication between neurons and will provide the basis for future studies of human mental health and behavioral disorders.

描述（由申请人提供）：神经元系统的标志在于元件之间巨大的、可修改的功能互连。了解大脑功能需要详细了解这种功能性连接是如何实现的，但用于分析清醒大脑中突触通信的工具非常有限。在体外，已经使用成对的细胞内记录或丘脑或其他传入的最小电刺激研究了细胞与细胞的连接。这些方法已经产生了大量关于细胞间相互作用的信息，但是体外切片消除了许多在完整大脑中运作的突触和调节输入。此外，这些方法难以应用于体内，其中用于检查突触相互作用的主要工具是细胞外互相关。上述体外工具以及体内细胞外互相关通常产生单个突触前神经元对单个（或对极少数）突触后靶细胞的突触影响的分析。然而，一些实验问题需要观察单个突触前神经元对其靶向皮质域产生的整体、全局突触影响。我们一直在开发一种方法，产生这样的观点，称为尖峰触发电流源密度分析。该方法允许分析由单个突触前神经元对包含在直径约200微米的受限皮质圆柱体内的神经元群体产生的突触影响。这种方法已被证明是非常有用的系统中，突触前神经元产生一个相对强大的和集中的影响的目标域的研究。拟议工作的目标是更好地了解这种方法的优势和局限性，并将其应用于大脑中更普遍的较弱和不太集中的神经元连接。通过这样做，拟议的工作将为科学界提供一个新的和强大的工具，用于研究完整的，清醒的大脑中的功能连接。目前的工作将对我们监测完整清醒大脑中功能性神经元连接的能力产生重要影响。神经交流的中断与一系列精神疾病有关。该提案涉及开发研究神经元之间通信的新方法，并将为未来研究人类心理健康和行为障碍提供基础。