Transgenic Dissection of the Neural Circuitry of the Intact Hippocampal Formation

University Of Oregon, Eugene OR

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Abstract

DESCRIPTION (provided by applicant): This application describes experiments that analyze the neural circuitry of the hippocampal formation (HF), the brain area most clearly implicated in memory and disorders such as Alzheimer's and related dementias. It combines neuron-specific transgene expression with electrophysiological techniques to study the transformation of information in the mammalian hippocampal formation at the cellular and network level. The approach is similar to the nodal analysis performed by engineers to analyze electronic circuits. Here, however, the nodes are neural cell types rather than electrical components. The nodes are specified by transgenic driver lines which direct the expression of various transgenes (depending upon which transgenic payload lines they are crossed to) enabling cell type specific changes in activity. Performing this nodal analysis, we manipulate the activity of one node while recording from others, much as when a potentiometer controlling the impedance of an amplifier circuit changes audio output when manipulated. We do so by driving the expression of transgenes which increase or decrease the membrane potential of neurons when activated either by specific drugs or wavelengths of light. We can then manipulate the activity of an identifiable population of primary neurons in the HF circuit while recording the activity of others gaining a functional understanding of how information is transformed from one region to the next.