title: Layer 2/3 pyramidal cells in the medial prefrontal cortex moderate stress induced depressive behaviors.
abstract: Major depressive disorder (MDD) is a prevalent illness that can be precipitated by acute or chronic stress. Studies of patients with Wolfram syndrome and carriers have identified Wfs1 mutations as causative for MDD. The medial prefrontal cortex (mPFC) is known to be involved in depression and behavioral resilience, although the cell types and circuits in the mPFC that moderate depressive behaviors in response to stress have not been determined. Here, we report that deletion of Wfs1 from layer 2/3 pyramidal cells impairs the ability of the mPFC to suppress stress-induced depressive behaviors, and results in hyperactivation of the hypothalamic-pituitary-adrenal axis and altered accumulation of important growth and neurotrophic factors. Our data identify superficial layer 2/3 pyramidal cells as critical for moderation of stress in the context of depressive behaviors and suggest that dysfunction in these cells may contribute to the clinical relationship between stress and depression.
authors.affiliation: Laboratory of Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States.
authors.forename: Prerana
authors.initials: P
authors.lastname: Shrestha
authors.affiliation: Laboratory of Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States.
authors.forename: Awni
authors.initials: A
authors.lastname: Mousa
authors.affiliation: Laboratory of Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Heintz
mesh_terms: D000818:Animals; D003863:Depression; D005260:Female; D055786:Gene Knockout Techniques; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D017397:Prefrontal Cortex / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D013315:Stress, Psychological
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein
keywords: anxiety; depression; layer 2/3; medial prefrontal cortex; mouse; neuroscience; stress; wolfram syndrome