title: Roles of p75(NTR), long-term depression, and cholinergic transmission in anxiety and acute stress coping.
abstract: BACKGROUND
  Stress is causally associated with anxiety. Although the underlying cellular mechanisms are not well understood, the basal forebrain cholinergic neurons have been implicated in stress response. p75(NTR) is a panneurotrophin receptor expressed almost exclusively in basal forebrain cholinergic neurons in adult brain. This study investigated whether and how p75(NTR), via regulation of the cholinergic system and hippocampal synaptic plasticity, influences stress-related behaviors.
  
  
  METHODS
  We used a combination of slice electrophysiology, behavioral analyses, pharmacology, in vivo microdialysis, and neuronal activity mapping to assess the role of p75(NTR) in mood and stress-related behaviors and its underlying cellular and molecular mechanisms.
  
  
  RESULTS
  We show that acute stress enables hippocampal long-term depression (LTD) in adult wild-type mice but not in mice lacking p75(NTR). The p75(NTR) mutant mice also exhibit two distinct behavioral impairments: baseline anxiety-like behavior and a deficit in coping with and recovering from stressful situations. Blockade of stress-enabled LTD with a GluA2-derived peptide impaired stress recovery without affecting baseline anxiety. Pharmacological manipulations of cholinergic transmission mimicked the p75(NTR) perturbation in both baseline anxiety and responses to acute stress. Finally, we show evidence of misregulated cholinergic signaling in animals with p75(NTR) deletion.
  
  
  CONCLUSIONS
  Our results suggest that loss of p75(NTR) leads to changes in hippocampal cholinergic signaling, which may be involved in regulation of stress-enabled hippocampal LTD and in modulating behaviors related to stress and anxiety.
authors: Mood and Anxiety Disorders Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors: Keri
authors: K
authors: Martinowich
authors: Robert J
authors: RJ
authors: Schloesser
authors: Yuan
authors: Y
authors: Lu
authors: Dennisse V
authors: DV
authors: Jimenez
authors: Daniel
authors: D
authors: Paredes
authors: Joshua S
authors: JS
authors: Greene
authors: Nigel H
authors: NH
authors: Greig
authors: Husseini K
authors: HK
authors: Manji
authors: Bai
authors: B
authors: Lu
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000223:Adaptation, Psychological / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D001703:Biophysics; D018678:Cholinergic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017551:Microdialysis; D008845:Microinjections; D016202:N-Methylaspartate / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000378:metabolism*; D013315:Stress, Psychological / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D018678:Cholinergic Agents; D016760:Proto-Oncogene Proteins c-fos; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D016202:N-Methylaspartate; D000109:Acetylcholine