Roles of p75NTR, Long-Term Depression, and Cholinergic Transmission in Anxiety and Acute Stress Coping
| Autor: | Husseini K. Manji, Joshua S. Greene, Nigel H. Greig, Keri Martinowich, Yuan Lu, Daniel Paredes, Bai Lu, Robert J. Schloesser, Dennisse V. Jimenez |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
N-Methylaspartate Patch-Clamp Techniques Time Factors Microinjections Microdialysis Biophysics Cholinergic Agents Receptors Nerve Growth Factor Anxiety In Vitro Techniques Hippocampal formation Hippocampus Article Mice Adaptation Psychological Animals Premovement neuronal activity Cholinergic neuron Maze Learning Long-term depression Long-Term Synaptic Depression Biological Psychiatry Mice Knockout Analysis of Variance Basal forebrain Dose-Response Relationship Drug biology Acetylcholine Electric Stimulation Mice Inbred C57BL Disease Models Animal nervous system Exploratory Behavior biology.protein Cholinergic Psychology Proto-Oncogene Proteins c-fos Neuroscience Stress Psychological Neurotrophin |
| Zdroj: | Biological Psychiatry. 71:75-83 |
| ISSN: | 0006-3223 |
| DOI: | 10.1016/j.biopsych.2011.08.014 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect