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

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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.