Kim, Y., Perova, Z., Mirrione, M. M., Pradhan, K., Henn, F. A., Shea, S., Osten, P., Li, B. (February 2016) Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression. Front Neural Circuits, 10. ISSN 1662-5110 (Electronic)1662-5110 (Linking)
Abstract
Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP - a marker of neuronal activation - in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing "helpless" behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing "resilient" behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | C-fos expression Positron-emission tomography depression learned helplessness serial two-photon tomography |
| Subjects: | diseases & disorders > mental disorders > mood disorders > depression Investigative techniques and equipment > Whole Brain Circuit Mapping |
| CSHL Authors: | |
| Communities: | CSHL labs > Henn lab CSHL labs > Li lab CSHL labs > Osten lab CSHL labs > Shea lab School of Biological Sciences > Publications |
| Depositing User: | Matt Covey |
| Date: | 3 February 2016 |
| Date Deposited: | 17 Feb 2016 21:49 |
| Last Modified: | 11 Jan 2019 21:48 |
| PMCID: | PMC4737884 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/32363 |
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