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

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. In conclusion, our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses tostress, and providemore » a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [4] ;  [4] ;  [4]
  1. Cold Spring Harbor Lab., Cold Spring Harbor, NY (United States); Penn State Univ., Hershey, PA (United States)
  2. Cold Spring Harbor Lab., Cold Spring Harbor, NY (United States); MRC Lab. of Molecular Biology, Cambridge (United Kingdom)
  3. Cold Spring Harbor Lab., Cold Spring Harbor, NY (United States); Brookhaven National Lab. (BNL), Upton, NY (United States); Quinnipiac Univ., Hamden, CT (United States)
  4. Cold Spring Harbor Lab., Cold Spring Harbor, NY (United States)
  5. Cold Spring Harbor Lab., Cold Spring Harbor, NY (United States); Brookhaven National Lab. (BNL), Upton, NY (United States); Mount Sinai School of Medicine, New York, NY (United States)
Publication Date:
Type:
Accepted Manuscript
Journal Name:
Frontiers in Neural Circuits
Additional Journal Information:
Journal Volume: 10; Journal ID: ISSN 1662-5110
Publisher:
Frontiers Research Foundation
Research Org:
Cold Spring Harbor Lab., Cold Spring Harbor, NY (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; C-fos expression; serial two-photon tomography; Positron-emission tomography; learned helplessness; depression
OSTI Identifier:
1378931