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The Journal of Neuroscience, July 21, 2004, 24(29):6466-6475; doi:10.1523/JNEUROSCI.4737-03.2004

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Cellular/Molecular
Alteration of Neuronal Firing Properties after In Vivo Experience in a FosGFP Transgenic Mouse

Alison L. Barth,^1,2 Richard C. Gerkin,² and Kathleen L. Dean^1,3

¹Department of Biological Sciences and Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, ²Department of Neurobiology and Center for Neuroscience at the University of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, and ³Department of Neuroscience and Behavior, Mount Holyoke College, South Hadley, Massachusetts 01075

Identifying the cells and circuits that underlie perception, behavior, and learning is a central goal of contemporary neuroscience. Although techniques such as lesion analysis, functional magnetic resonance imaging, 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 for the identification and electrophysiological characterization of individual neurons that are associated with a particular function in living tissue. We developed a strain of transgenic mice in which the expression of the green fluorescent protein (GFP) is controlled by the promoter of the activity-dependent gene c-fos. These mice enable an in vivo or ex vivo characterization of the cells and synapses that are activated by particular pharmacological and behavioral manipulations. Cortical and subcortical fosGFP expression could be induced in a regionally restricted manner after specific activation of neuronal ensembles. Using the fosGFP mice to identify discrete cortical areas, we found that neurons in sensory-spared areas rapidly regulate action potential threshold and spike frequency to decrease excitability. This method will enhance our ability to study the way neuronal networks are activated and changed by both experience and pharmacological manipulations. In addition, because activated neurons can be functionally characterized, this tool may enable the development of better pharmaceuticals that directly affect the neurons involved in disease states.

Key words: hypothalamus; schizophrenia; transcription; c-fos; GFP; transgenic; activity-dependent; in vivo; barrel cortex; drug discovery

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Received Oct 20, 2003; revised May 12, 2004; accepted May 13, 2004.

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