Basolateral amygdala noradrenergic activity mediates corticosterone-induced enhancement of auditory fear conditioning

Roozendaal, Benno; Hui, Gabriel K.; Hui, Isabel R.; Berlau, Daniel J.; McGaugh, James L.; Weinberger, Norman M.

doi:10.1016/j.nlm.2006.03.003

Cited by 169 publications

(109 citation statements)

References 41 publications

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“…Corticosterone also exerts effects within the amygdala via actions at glucocorticoid receptors (Aronsson et al, 1988). Of particular interest in this context, BLA has been identified as a critical site of action through which glucocorticoids modulate associative fear memory, (for example) glucocorticoid receptor agonists administered systemically or directly into the BLA enhance fear conditioning in rats (Zorawski and Killcross, 2002;Hui et al, 2004;Roozendaal et al, 2006). This raises the possibility that increased glucocorticoid receptor activity in smaller BLA mice may be a factor driving enhanced fear conditioning, although this remains to be tested.…”

Section: Discussionmentioning

confidence: 99%

Variation in Mouse Basolateral Amygdala Volume is Associated With Differences in Stress Reactivity and Fear Learning

Yang

Mozhui

Karlsson

et al. 2008

Neuropsychopharmacol

133

106

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A wealth of research identifies the amygdala as a key brain region mediating negative affect, and implicates amygdala dysfunction in the pathophysiology of anxiety disorders. Although there is a strong genetic component to anxiety disorders such as posttraumatic stress disorder (PTSD) there remains debate about whether abnormalities in amygdala function predispose to these disorders. In the present study, groups of C57BL/6 Â DBA/2 (B Â D) recombinant inbred strains of mice were selected for differences in volume of the basolateral amygdala complex (BLA). Strains with relatively small, medium, or large BLA volumes were compared for Pavlovian fear learning and memory, anxiety-related behaviors, depression-related behavior, and glucocorticoid responses to stress. Strains with relatively small BLA exhibited stronger conditioned fear responses to both auditory tone and contextual stimuli, as compared to groups with larger BLA. The small BLA group also showed significantly greater corticosterone responses to stress than the larger BLA groups. BLA volume did not predict clear differences in measures of anxiety-like behavior or depression-related behavior, other than greater locomotor inhibition to novelty in strains with smaller BLA. Neither striatal, hippocampal nor cerebellar volumes correlated significantly with any behavioral measure. The present data demonstrate a phenotype of enhanced fear conditioning and exaggerated glucocorticoid responses to stress associated with small BLA volume. This profile is reminiscent of the increased fear processing and stress reactivity that is associated with amygdala excitability and reduced amygdala volume in humans carrying loss of function polymorphisms in the serotonin transporter and monoamine oxidase A genes. Our study provides a unique example of how natural variation in amygdala volume associates with specific fear-and stress-related phenotypes in rodents, and further supports the role of amygdala dysfunction in anxiety disorders such as PTSD.

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Section: Discussionmentioning

confidence: 99%

Variation in Mouse Basolateral Amygdala Volume is Associated With Differences in Stress Reactivity and Fear Learning

Yang

Mozhui

Karlsson

et al. 2008

Neuropsychopharmacol

133

106

View full text Add to dashboard Cite

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“…Whereas the slow genomic effects promote reinstalling homeostasis in humans and rodents (presumably GR-mediated, Henckens et al, 2011;Herman et al, 2012), rapid non-genomic (MR-mediated) effects seem to enhance catecholaminergic effects within minutes, for example, by enhancing excitability of the amygdala in vitro (Karst et al, 2010). Studies investigating emotional memories in rodents have already demonstrated that both stress-systems have synergistic effects in the amygdala (eg, Roozendaal et al, 2006). Importantly, we did not measure NE levels directly.…”

Section: Effects Of Mineralocorticoid Receptor Blocking In Humans S Vmentioning

confidence: 98%

Blocking the Mineralocorticoid Receptor in Humans Prevents the Stress-Induced Enhancement of Centromedial Amygdala Connectivity with the Dorsal Striatum

Vogel

Klumpers

Krugers

et al. 2014

Neuropsychopharmacol

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Two research lines argue for rapid stress-induced reallocations of neural network activity involving the amygdala. One focuses on the role of norepinephrine (NE) in mediating a shift towards the salience network and improving vigilance processing, whereas the other focuses on the role of cortisol in enhancing automatic, habitual responses. It has been suggested that the mineralocorticoid receptor (MR) is critical in shifting towards habitual responses, which are supported by the dorsal striatum. However, until now it remained unclear whether these two reallocations of neural recourses might be part of the same phenomenon and develop immediately after stress onset. We combined methods used in both approaches and hypothesized specifically that stress would lead to rapidly enhanced involvement of the striatum as assessed by amygala-striatal connectivity. Furthermore, we tested the hypothesis that this shift depends on cortisol interacting with the MR, by using a randomized, placebo-controlled, full-factorial, between-subjects design with the factors stress and MRblockade (spironolactone). We investigated 101 young, healthy men using functional magnetic resonance imaging after stress induction, which led to increased negative mood, heart rate, and cortisol levels. We confirmed our hypothesis by revealing a stress-by-MR-blockade interaction on the functional connectivity between the centromedial amygdala (CMA) and the dorsal striatum. Stress rapidly enhanced CMA-striatal connectivity and this effect was correlated with the stress-induced cortisol response, but required MR availability. This finding might suggest that the stress-induced shift described by distinct research lines might capture different aspects of the same phenomenon, ie, a reallocation of neural resources coordinated by both NE and cortisol. Neuropsychopharmacology (2015) 40, 947-956;

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“…In rodents, corticosterone has been implicated in LTM formation of contextual fear memory (Pugh et al 1997;Thompson et al 2004) and tone-specific cued fear memory (Hui et al 2004;Roozendaal et al 2006;Marchand et al 2007). We aimed to investigate how nNOS gene deletion might affect the physiological response to fear conditioning.…”

Section: Corticosteronementioning

confidence: 99%

Impairments in fear conditioning in mice lacking the nNOS gene

et al. 2009

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The fear conditioning paradigm is used to investigate the roles of various genes, neurotransmitters, and substrates in the formation of fear learning related to contextual and auditory cues. In the brain, nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) functions as a retrograde neuronal messenger that facilitates synaptic plasticity, including the late phase of long-term potentiation (LTP) and formation of long-term memory (LTM). Evidence has implicated NO signaling in synaptic plasticity and LTM formation following fear conditioning, yet little is known about the role of the nNOS gene in fear learning. Using knockout (KO) mice with targeted mutation of the nNOS gene and their wild-type (WT) counterparts, the role of NO signaling in fear conditioning was investigated. Plasma levels of the stress hormone corticosterone were measured to determine the relationship between physiological and behavioral response to fear conditioning. Contextual fear learning was severely impaired in male and female nNOS KO mice compared with WT counterparts; cued fear learning was slightly impaired in nNOS KO mice. Sex-dependent differences in both contextual and cued fear learning were not observed in either genotype. Deficits in contextual fear learning in nNOS KO mice were partially overcome by multiple trainings. A relationship between increase in plasma corticosterone levels following footshock administration and the magnitude of contextual, but not cued freezing was also observed. Results suggest that the nNOS gene contributes more to optimal contextual fear learning than to cued fear learning, and therefore, inhibition of the nNOS enzyme may ameliorate context-dependent fear response.Anxiety disorders, such as post-traumatic stress disorder (PTSD), constitute the most prevalent mental illnesses in the United States, costing nearly one-third of the country's total health bill (Greenberg et al. 1999). The treatment of these disorders requires overcoming complications such as reluctance to seek mental health treatment and an extremely high comorbidity rate with other affective disorders, reaching 80% (Brady 1997;Solomon and Davidson 1997). Emerging evidence suggests that dysfunctions underlying acquired anxiety and PTSD include an abnormal reaction to stress, which is mediated by specific neurochemical and neuroanatomical substrates (Yehuda and McFarlane 1995;Adamec 1997). Pharmacotherapies that target neuronal signaling molecules, such as nitric oxide (NO), may play a role in the treatment of these disorders.In the brain, N-methyl-D-aspartate receptor (NMDAR) activation and calcium influx into the cell activates the neuronal nitric oxide synthase (nNOS) enzyme to produce NO, which has the role of retrograde messenger (Snyder 1992). NO is involved in memory formation and synaptic plastic events such as late-phase long-term potentiation (LTP) (Lu et al. 1999;Arancio et al. 2001;Puzzo et al. 2006). Behavioral evidence in invertebrates (Lewin and Walters 1999;Muller 2000;Kemenes et al. 2002;Matsumoto et al. 2006) ...

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Basolateral amygdala noradrenergic activity mediates corticosterone-induced enhancement of auditory fear conditioning

Cited by 169 publications

References 41 publications

Variation in Mouse Basolateral Amygdala Volume is Associated With Differences in Stress Reactivity and Fear Learning

Variation in Mouse Basolateral Amygdala Volume is Associated With Differences in Stress Reactivity and Fear Learning

Blocking the Mineralocorticoid Receptor in Humans Prevents the Stress-Induced Enhancement of Centromedial Amygdala Connectivity with the Dorsal Striatum

Impairments in fear conditioning in mice lacking the nNOS gene

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