High-speed imaging reveals neurophysiological links to behavior in an animal model of depression.
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.
Airan
Raag D
RD
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Meltzer
Leslie A
LA
Roy
Madhuri
M
Gong
Yuqing
Y
Chen
Han
H
Deisseroth
Karl
K
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D003866:Depressive Disorder / Q000473:pathology / Q000503:physiopathology*; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D007099:Imipramine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009415:Nerve Net / Q000503:physiopathology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology
D000929:Antidepressive Agents, Tricyclic; D005473:Fluoxetine; D007099:Imipramine; D017367:Selective Serotonin Reuptake Inhibitors