title: Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression.
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.
authors: Cold Spring Harbor LaboratoryCold Spring Harbor, NY, USA; Department of Neural and Behavioral Sciences, College of Medicine, Penn State UniversityHershey, PA, USA.
authors: Yongsoo
authors: Y
authors: Kim
authors: Cold Spring Harbor LaboratoryCold Spring Harbor, NY, USA; MRC Laboratory of Molecular BiologyCambridge, UK.
authors: Zinaida
authors: Z
authors: Perova
authors: Cold Spring Harbor LaboratoryCold Spring Harbor, NY, USA; Medical Department, Brookhaven National LaboratoryUpton, NY, USA; Department of Biomedical Sciences, Quinnipiac UniversityHamden, CT, USA.
authors: Martine M
authors: MM
authors: Mirrione
authors: Cold Spring Harbor Laboratory Cold Spring Harbor, NY, USA.
authors: Kith
authors: K
authors: Pradhan
authors: Cold Spring Harbor LaboratoryCold Spring Harbor, NY, USA; Medical Department, Brookhaven National LaboratoryUpton, NY, USA; Psychiatry Department, Mount Sinai School of MedicineNew York, NY, USA.
authors: Fritz A
authors: FA
authors: Henn
authors: Cold Spring Harbor Laboratory Cold Spring Harbor, NY, USA.
authors: Stephen
authors: S
authors: Shea
authors: Cold Spring Harbor Laboratory Cold Spring Harbor, NY, USA.
authors: Pavel
authors: P
authors: Osten
authors: Cold Spring Harbor Laboratory Cold Spring Harbor, NY, USA.
authors: Bo
authors: B
authors: Li
mesh_terms: D000818:Animals; D001703:Biophysics; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D003863:Depression / Q000473:pathology*; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006380:Helplessness, Learned; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D049268:Positron-Emission Tomography; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D019788:Fluorodeoxyglucose F18; D049452:Green Fluorescent Proteins
keywords: C-fos expression; Positron-emission tomography; depression; learned helplessness; serial two-photon tomography