Neuronal hypertrophy dampens neuronal intrinsic excitability and stress responsiveness during chronic stress

Autor: Mathilde S. Henry, Hiroyuki Igarashi, Xue Fang Wang, Sara Matovic, Marie-Ève Tremblay, Eric W Salter, Eric S. Kuebler, Wataru Inoue, Nathalie Vernoux, Aoi Ichiyama, Julia K. Sunstrum, Julio Martinez-Trujillo
Přispěvatelé: University of Western Ontario (UWO), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval)
Rok vydání: 2020
Předmět:
Zdroj: J Physiol
The Journal of Physiology
The Journal of Physiology, Wiley, 2020, 598 (13), pp.2757-2773. ⟨10.1113/JP279666⟩
Physiology and Pharmacology Publications
ISSN: 1469-7793
0022-3751
Popis: © 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society Key points: The hypothalamic-pituitary-adrenal (HPA) axis habituates to repeated stress exposure. We studied hypothalamic corticotropin-releasing hormone (CRH) neurons that form the apex of the HPA axis in a mouse model of stress habituation using repeated restraint. The intrinsic excitability of CRH neurons decreased after repeated stress in a time course that coincided with the development of HPA axis habituation. This intrinsic excitability plasticity co-developed with an expansion of surface membrane area, which increased a passive electric load and dampened membrane depolarization in response to the influx of positive charge. We report a novel structure–function relationship for intrinsic excitability plasticity as a neural correlate for HPA axis habituation. Abstract: Encountering a stressor immediately activates the hypothalamic-pituitary-adrenal (HPA) axis, but this stereotypic stress response also undergoes experience-dependent adaptation. Despite the biological and clinical importance, how the brain adjusts stress responsiveness in the long term remains poorly understood. We studied hypothalamic corticotropin-releasing hormone neurons that form the apex of the HPA axis in a mouse model of stress habituation using repeated restraint. Using patch-clamp electrophysiology in acute slices, we found that the intrinsic excitability of these neurons substantially decreased after daily repeated stress in a time course that coincided with their loss of stress responsiveness in vivo. This intrinsic excitability plasticity co-developed with an expansion of surface membrane area, which increased a passive electric load, and dampened membrane depolarization in response to the influx of positive charge. Multiphoton imaging and electron microscopy revealed that repeated stress augmented ruffling of the plasma membrane, suggesting an ultrastructural plasticity that may efficiently accommodate the membrane area expansion. Overall, we report a novel structure–function relationship for intrinsic excitability plasticity as a neural correlate for adaptation of the neuroendocrine stress response.
Databáze: OpenAIRE
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