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High-Speed Imaging Reveals Neurophysiological Links to Behavior in an Animal Model of Depression
Raag D. Airan,1*Leslie A. Meltzer,2*Madhuri Roy,1Yuqing Gong,3,4Han Chen,3Karl Deisseroth1,5
The hippocampus is one of several brain areas thought to playa central role in affective behaviors, but the underlying localnetwork dynamics are not understood. We used quantitative voltage-sensitivedye imaging to probe hippocampal dynamics with millisecond resolutionin brain slices after bidirectional modulation of affectivestate in rat models of depression. We found that a simple measureof real-time activity—stimulus-evoked percolation of activitythrough the dentate gyrus relative to the hippocampal outputsubfield—accounted for induced changes in animal behaviorindependent of the underlying mechanism of action of the treatments.Our results define a circuit-level neurophysiological endophenotypefor affective behavior and suggest an approach to understandingcircuit-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.
To whom correspondence should be addressed. E-mail: deissero{at}stanford.edu
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