title: Endocannabinoid signaling within the basolateral amygdala integrates multiple stress hormone effects on memory consolidation.
abstract: Glucocorticoid hormones are known to act synergistically with other stress-activated neuromodulatory systems, such as norepinephrine and corticotropin-releasing factor (CRF), within the basolateral complex of the amygdala (BLA) to induce optimal strengthening of the consolidation of long-term memory of emotionally arousing experiences. However, as the onset of these glucocorticoid actions appear often too rapid to be explained by genomic regulation, the neurobiological mechanism of how glucocorticoids could modify the memory-enhancing properties of norepinephrine and CRF remained elusive. Here, we show that the endocannabinoid system, a rapidly activated retrograde messenger system, is a primary route mediating the actions of glucocorticoids, via a glucocorticoid receptor on the cell surface, on BLA neural plasticity and memory consolidation. Furthermore, glucocorticoids recruit downstream endocannabinoid activity within the BLA to interact with both the norepinephrine and CRF systems in enhancing memory consolidation. These findings have important implications for understanding the fine-tuned crosstalk between multiple stress hormone systems in the coordination of (mal)adaptive stress and emotional arousal effects on neural plasticity and memory consolidation.
authors.affiliation: 1] Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, The Netherlands [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Piray
authors.initials: P
authors.lastname: Atsak
authors.affiliation: 1] Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, The Netherlands [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands [3] Department of Anaesthesiology, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Hauer
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.affiliation: Department of Anaesthesiology, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Gustav
authors.initials: G
authors.lastname: Schelling
authors.affiliation: Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, Brazil.
authors.forename: Raquel V
authors.initials: RV
authors.lastname: Fornari
authors.affiliation: 1] Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, The Netherlands [2] Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Benno
authors.initials: B
authors.lastname: Roozendaal
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000502:physiology*; D002408:Catheters, Indwelling; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004597:Electroshock; D063388:Endocannabinoids / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D063388:Endocannabinoids; D005938:Glucocorticoids; D003346:Corticotropin-Releasing Hormone; D009638:Norepinephrine