Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression

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)

URL: http://www.ncbi.nlm.nih.gov/pubmed/26869888
DOI: 10.3389/fncir.2016.00003


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

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving