Identifying the cells and circuits that underlie perception, behavior, and learning is a central goal of contemporary neuroscience. Although techniques such as lesion analysis, fMRI, 2-deoxyglucose studies, and induction of gene expression have been helpful in determining the brain areas responsible for particular functions, these methods are technically limited. Currently there is no method that allows the identification of individual neurons that are associated with a particular function in living tissue. We have developed a strain of transgenic mice in which the expression of green fluorescent protein (GFP) is controlled by the promoter of the activity-dependent gene c-fos. Cortical and subcortical fosGFP expression could be induced in a regionally restricted fashion following specific activation of neuronal ensembles. This proposal seeks to further characterize the fosGFP transgenic mouse and validate this tool as a method for anatomical and electrophysiological analysis of neuronal subsets activated by in vivo experience. Single whisker stimulation induces c-fos and fosGFP expression in a cortical whisker barrel during experience-dependent plasticity. In order to better understand how neuronal gene expression in activated subsets of neurons leads to expansion of receptive fields for spared sensory inputs, fosGFP fluorescent neurons will be targeted for whole-cell recording. The fosGFP mice will be used to understand the anatomical and synaptic changes that underlie experience-dependent plasticity. These mice enable an in vivo or ex vivo characterization of the cells and synapses activated by particular pharmacological and behavioral manipulations. This method will enhance our ability to study the way neuronal networks are activated and changed by both experience and pharmacological manipulations.
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