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Functional analysis of neural circuits identified by molecular markers and trans-synaptic tracers


Local neural circuits form the modules of brain function. For example, in the visual system we find individual modules that are specialized to detect the orientation of objects, the colour, the presence of edges, or the direction of movement. The output and therefore the functional property of each module are determined by the interactions of the neurons within the modules. Despite their omnipresence, however, very little is known about the functional properties of local circuits.

Their systematic investigation has been hindered by the sheer number of cells, and by the diversity especially of interneurons. This made repeated and reliable recordings from neurons of an identified circuit almost impossible. In this proposal I describe a novel and multidisciplina ry approach which overcomes this problem. It combines methods using transgenic mice, viruses and molecular biology (to label specific circuits) with electrophysiology and functional imaging (to monitor the activity of the labelled cells).

This combination o f methods from diverse fields of biology creates a synergy that allows me to address questions which were previously inaccessible. I can record simultaneously from a population of cells of a single type to assess the encoding of a sensory stimulus in that cell type, and to judge the variability that exists in neural processing; I can asses the role of a cell type by recording from circuits in which I have eliminated this cell type; and I can follow information transmission and processing through every cell of a given circuit by singly or simultaneously recording from different cells in that circuit. Results from this project can also be applied to technical application, for example by building bio-inspired electronic circuits that mimic the computational lay out of the brain to efficiently solve computational problems.

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