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Originally published in Science Express on 5 July 2007
Science 10 August 2007:
Vol. 317. no. 5839, pp. 819 - 823
DOI: 10.1126/science.1144400
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Reports

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 Yuqing Gong,3,4 Han Chen,3 Karl Deisseroth1,5{dagger}

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 after bidirectional modulation of affective state in rat 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 circuit-level neurophysiological endophenotype for affective behavior and suggest an approach to understanding circuit-level substrates underlying psychiatric disease symptoms.

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.
4 Department of Statistics, Stanford University, Stanford, CA 94305, USA.
5 Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: deissero{at}stanford.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)