Role of adrenal stress hormones in forming lasting memories in the brain

McGaugh, James L.; Roozendaal, Benno

doi:10.1016/s0959-4388(02)00306-9

Cited by 735 publications

(516 citation statements)

References 72 publications

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“…To our knowledge, this is the first report of perturbation in this type of memory in the early phase of AD in AD mice, as few other studies tested this mnemonic deficit at more advanced stages of the pathology (Baglietto-Vargas et al, 2013;Davis et al, 2013;Good et al, 2007). In light of the impaired HPA axis feedback and the key role played by CORT in facilitating the consolidation of emotionally-charged memories (McGaugh and Roozendaal, 2002), it was crucial to monitor episodic memories in minimized stress conditions as presented here. We can therefore attribute the observed memory deficit to a prolonged dysregulation of the HPA axis accompanied by APP misprocessing and not to acute changes in CORT levels induced by the design of the behavioral paradigm.…”

Section: Discussionmentioning

confidence: 88%

Subchronic Glucocorticoid Receptor Inhibition Rescues Early Episodic Memory and Synaptic Plasticity Deficits in a Mouse Model of Alzheimer’s Disease

Lanté

Chafaï

Raymond

et al. 2015

Neuropsychopharmacol

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The early phase of Alzheimer's disease (AD) is characterized by hippocampus-dependent memory deficits and impaired synaptic plasticity. Increasing evidence suggests that stress and dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis, marked by the elevated circulating glucocorticoids, are risk factors for AD onset. How these changes contribute to early hippocampal dysfunction remains unclear. Using an elaborated version of the object recognition task, we carefully monitored alterations in key components of episodic memory, the first type of memory altered in AD patients, in early symptomatic Tg2576 AD mice. We also combined biochemical and ex vivo electrophysiological analyses to reveal novel cellular and molecular dysregulations underpinning the onset of the pathology. We show that HPA axis, circadian rhythm, and feedback mechanisms, as well as episodic memory, are compromised in this early symptomatic phase, reminiscent of human AD pathology. The cognitive decline could be rescued by subchronic in vivo treatment with RU486, a glucocorticoid receptor antagonist. These observed phenotypes were paralleled by a specific enhancement of N-Methyl-D-aspartic acid receptor (NMDAR)-dependent LTD in CA1 pyramidal neurons, whereas LTP and metabotropic glutamate receptor-dependent LTD remain unchanged. NMDAR transmission was also enhanced. Finally, we show that, as for the behavioral deficit, RU486 treatment rescues this abnormal synaptic phenotype. These preclinical results define glucocorticoid signaling as a contributing factor to both episodic memory loss and early synaptic failure in this AD mouse model, and suggest that glucocorticoid receptor targeting strategies could be beneficial to delay AD onset.

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Section: Discussionmentioning

confidence: 88%

Subchronic Glucocorticoid Receptor Inhibition Rescues Early Episodic Memory and Synaptic Plasticity Deficits in a Mouse Model of Alzheimer’s Disease

Lanté

Chafaï

Raymond

et al. 2015

Neuropsychopharmacol

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“…In an extensive series of studies conducted primarily in the inhibitory avoidance paradigm, glucocorticoid release has been implicated in the formation and consolidation of fear memories. 255 Upon being released by the adrenal gland, corticosterone (in rats) or cortisol (in humans) freely crosses the blood-brain barrier and binds to glucocorticoid receptors (GRs) in brain regions including the nucleus of the solitary tract, hippocampus, and amygdala, where it modulates memory formation. Post-training administration of the synthetic glucocorticoid dexamethasone facilitates memory, whereas administration of the corticosterone synthesis inhibitor metyrapone impairs memory.…”

Section: Neurotransmitter Systemsmentioning

confidence: 99%

Mechanisms of fear extinction

2006

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Excessive fear and anxiety are hallmarks of a variety of disabling anxiety disorders that affect millions of people throughout the world. Hence, a greater understanding of the brain mechanisms involved in the inhibition of fear and anxiety is attracting increasing interest in the research community. In the laboratory, fear inhibition most often is studied through a procedure in which a previously fear conditioned organism is exposed to a fear-eliciting cue in the absence of any aversive event. This procedure results in a decline in conditioned fear responses that is attributed to a process called fear extinction. Extensive empirical work by behavioral psychologists has revealed basic behavioral characteristics of extinction, and theoretical accounts have emphasized extinction as a form of inhibitory learning as opposed to an erasure of acquired fear. Guided by this work, neuroscientists have begun to dissect the neural mechanisms involved, including the regions in which extinction-related plasticity occurs and the cellular and molecular processes that are engaged. The present paper will cover behavioral, theoretical and neurobiological work, and will conclude with a discussion of clinical implications. Molecular Psychiatry (2007) 12, 120-150.

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“…Noradrenergic neurons in the locus coeruleus project to many forebrain regions. Animal studies showed that corticosterone and norepinephrine (NE) act together to facilitate memory formation through actions involving the amygdala, hippocampus, and prefrontal cortex (PFC) [10,12]. More recently, glucocorticoids and the noradrenergic system were shown to interact in the medial PFC in producing working memory impairment [13].…”

Section: Stress Mediators: Glucocorticoids and Norepinephrinementioning

confidence: 99%

Neural mechanisms and computations underlying stress effects on learning and memory

Luksys

Sandi

2011

Current Opinion in Neurobiology

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Stress has complex effects on memory function that can vary depending on the type of information that is learned and in relation to inter-individual characteristics. Recent work has also shown that stress can switch performance between memory systems, biasing it toward habit in detriment of spatial or goaldirected strategies. In addition, novel synaptic mechanisms have been implicated in the effects of stress in plasticity and memory. Computational modeling is emerging as a useful approach to integrate and to ascertain neural and cognitive computations underlying different effects of stress in memory. Having provided novel explanations for the inverted-U-shaped relationship between stress and cognitive performance, modelbased analysis studies can improve our understanding of diverse effects of stress in cognition and psychopathology. IntroductionStress can have profound effects on memory function, both when chronically experienced and when acutely coupled with a cognitive challenge [1]. In this review, we mainly focus on the effects of acute stress on learning, memory, and underlying mechanisms. We will also examine new modeling approaches aiming to ascertain the neural computations that underlie stress effects in these cognitive processes.It is generally accepted that acute stress or elevated stress hormones facilitate memory consolidation while impairing the retrieval of information [2]. Moreover, acute stress is generally highly disruptive for working memory processing, while it can facilitate implicit learning [1,2,3 ]. Recently, several animal and human studies showed that stress switches performance between memory systems, promoting a transition from 'flexible' spatial or goaldirected learning to 'rigid' habitual stimulus-response (S-R) cognitive strategies [4 ,5 ,6,7].However, one should be cautious when summarizing the effects of stress on a particular memory process as either positive or negative. Stress is not a unitary process, with its duration, intensity, or timing with regards to the cognitive challenge being critical for its cognitive outcome [1]. In particular, stress intensity has been long recognized in the literature as highly relevant, with the predominant belief that an inverted-U-shaped function can explain the relationship between stress intensity and memory (i.e. low and high stress levels impairing memory, whereas intermediate levels facilitating it). Strikingly, despite the popularity of this hypothesis, experimental evidence supporting the existence of an inverted-U-shaped relationship for performance of rats in a hippocampal learning task under the same experimental conditions was presented only recently [8]. Stress mediators: glucocorticoids and norepinephrineGlucocorticoids and the noradrenergic system have been identified as key mediators of the cognitive effects of stress [1,2,9,10]. Adrenal glucocorticoids, steroid hormones produced by the adrenal glands, can cross the blood-brain barrier, gaining access to the brain. Through the binding to specific receptors, glucocorticoids ca...

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Role of adrenal stress hormones in forming lasting memories in the brain

Cited by 735 publications

References 72 publications

Subchronic Glucocorticoid Receptor Inhibition Rescues Early Episodic Memory and Synaptic Plasticity Deficits in a Mouse Model of Alzheimer’s Disease

Subchronic Glucocorticoid Receptor Inhibition Rescues Early Episodic Memory and Synaptic Plasticity Deficits in a Mouse Model of Alzheimer’s Disease

Mechanisms of fear extinction

Neural mechanisms and computations underlying stress effects on learning and memory

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