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

描述（由申请人提供）：神经元系统的特征在于元素之间巨大的、可修改的功能互联。了解大脑功能需要详细了解这种功能连接是如何实现的，但是分析清醒大脑中突触通信的工具非常有限。在体外，利用成对的细胞内记录或对丘脑或其他传入事件的最小电刺激，研究了细胞间的连通性。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，这些方法很难应用于体内，在体内，检查突触相互作用的主要工具是细胞外相互关联。上述体外工具，以及体内的细胞外相互关联，通常产生单个突触前神经元对单个（或极少数）突触后靶细胞的突触影响的分析。然而，一些实验问题需要对单个突触前神经元对其目标皮质区域产生的整体、全局突触影响进行观察。我们一直在开发一种方法来产生这样的视图，称为尖峰触发电流源密度分析。这种方法允许分析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产生的突触影响。这种方法在研究突触前神经元对目标区域产生相对强大和集中影响的系统中被证明是非常有用的。这项工作的目标是更好地理解这种方法的优点和局限性，并将其应用于大脑中更为普遍的较弱和较少聚焦的神经元连接。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来研究完整的，清醒的大脑的功能连接。目前的工作将对我们监测完整的、清醒的大脑中功能性神经元连接的能力产生重要影响。神经交流的中断与许多精神疾病有关。这一建议涉及到研究神经元之间交流的新方法的发展，并将为未来人类心理健康和行为障碍的研究提供基础。

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.