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Published Online July 5, 2007
Science DOI: 10.1126/science.1144400

Reports

Submitted on April 30, 2007
Accepted on June 28, 2007

High-Speed Imaging Reveals Neurophysiological Links to Behavior in an Animal Model of Depression

Raag D. Airan 1, Leslie A. Meltzer 2, Madhuri Roy 1, Madhuri Roy 1, Yuqing Gong 3, Han Chen 4, Karl Deisseroth 5*

1 Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
2 Neuroscience Program, Stanford University, Stanford, CA 94305, USA.
3 Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Statistics, Stanford University, Stanford, CA 94305, USA.
4 Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
5 Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.

* To whom correspondence should be addressed.
Karl Deisseroth , E-mail: deissero{at}stanford.edu

The hippocampus is one of several brain areas thought to play a central role in affective behaviors, but the underlying local network dynamics are not understood. We used quantitative voltage-sensitive dye imaging to probe hippocampal dynamics with millisecond resolution in brain slices following bidirectional modulation of affective state in rodent models of depression. We found that a simple measure of real-time activity, stimulus-evoked percolation of activity through the dentate gyrus relative to the hippocampal output subfield, accounted for induced changes in animal behavior independent of the underlying mechanism of action of the treatments. Our results define a network-level neurophysiological endophenotype for affective behavior and suggest an approach to understanding circuit-level substrates underlying psychiatric disease symptoms.


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