Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning

Kolber, Benedict J.; Roberts, Marie S.; Howell, Maureen P.; Wozniak, David F.; Sands, Mark S.; Muglia, Louis J.

doi:10.1073/pnas.0803216105

Cited by 118 publications

(112 citation statements)

References 34 publications

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“…Further investigations of interactions between the BLA and CEA as well as other fear-related circuitry, such as the bed nuclei of the stria terminalis and ventral medial hypothalamus, could provide a more detailed analysis of neural circuits underlying fear conditioning. Interestingly, all 4 of these regions, which receive afferents from the hippocampus and send projections to the ventral periaqueductal gray (the final output in the expression of freezing), express CRH receptors and, if lesioned, attenuate fear responding (32)(33)(34)(35)(36). Our data are consistent with the suggestion that plasticity in regions outside of the BLA can support the acquisition of fear (24,25).…”

Section: Discussionsupporting

confidence: 81%

“…In addition, Maren and colleagues (25) demonstrated that permanent or reversible lesions of the CEA disrupted the development of contextual fear conditioning, despite use of an overtraining procedure similar to the one used in the present study. Moreover, a recent paper by Kolber et al (32) showed that the specific deletion CEA glucocorticoid receptors disrupted fear acquisition and could be subsequently rescued by intracranial ventricular infusions of corticotrophin releasing hormone (CRH). The findings presented here, and previous studies indicating a role of the CEA, suggest a reevaluation of the present serial model of fear conditioning and a possible dissociation of the contributions of the CEA and BLA in the acquisition and storage of fear memories.…”

Section: Discussionmentioning

confidence: 99%

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Persistence of fear memory across time requires the basolateral amygdala complex

Poulos

Sterlace

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Mammals evolved a potent fear-motivated defensive system capable of single-trial fear learning that shows no forgetting over the lifespan of the animal. The basolateral amygdala complex (BLA) is considered an essential component of this conditional fear learning system. However, recent studies challenge this view and suggest that plasticity within other brain regions (i.e., central nucleus of the amygdala) may be crucial for fear conditioning. In the present study, we examine the mnemonic limits of contextual fear conditioning in the absence of the BLA using overtraining and by measuring remote fear memories. After excitotoxic lesions of the BLA were created, animals underwent overtraining and were tested at recent and remote memory intervals. Here we show that animals with BLA lesions can learn normal levels of fear. However, this fear memory loses its adaptive features: it is acquired slowly and shows substantial forgetting when remote memory is tested. Collectively, these findings suggest that fear-related plasticity acquired by brain regions outside of the BLA, unlike those acquired in the intact animals, do so for a relatively time-limited period.fear conditioning ͉ forgetting ͉ remote memory ͉ savings F ailure to defend against an environmental threat such as predation exacts an extreme cost on adaptive fitness (1). Unlike a single missed feeding or mating opportunity, a single failure to defend means you will have no future opportunities to pass on your genes. As a consequence, mammals have evolved a potent fear-motivated defensive system that is capable of singletrial learning (2) and shows no forgetting over the lifespan of the animal (3). Prior studies suggest that such memories are normally established and permanently maintained within the basolateral complex of the amygdala (BLA) (3-7). Typically, damage to the BLA eliminates the acquisition and expression of Pavlovian fear memories across a wide spectrum of mammals, including humans (8) and rodents (5, 6, 9-13). Both electrophysiological and molecular markers of neural activity within the BLA reveal a learning-and retrieval-specific pattern of activation (14-18). Moreover, blockade of NMDA receptors or de novo protein synthesis within the BLA disrupts the acquisition and consolidation of fear memories (19)(20)(21)(22)(23). In addition, regardless of whether fear memories are 1 day or 1.5 years old, posttraining BLA lesions completely abolish the expression of fear (3). Collectively, such findings are consistent with a mnemonic role of the BLA in fear learning.However, recent studies have challenged this view and suggest that plasticity in other brain regions are capable of supporting fear conditioning (24,25). Indeed, there is growing evidence that fear conditioning can be established in the absence of the BLA. In particular, deficits resulting from either lesions or inactivations of the BLA can be overcome with extensive overtraining (7,(25)(26)(27). Furthermore, both Zimmerman et al. (25) and Wilensky et al. (24) have recently shown that disrup...

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Persistence of fear memory across time requires the basolateral amygdala complex

Poulos

Sterlace

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…In the same model, elevation of amygdala CORT increased corticotrophinreleasing factor (CRF) mRNA in the CeA and the BNST (37, 38). Thus, although clinical and preclinical evidence implicates important roles of stress activation of the CeA and BNST in GI pathologies, the mechanism of activation and interaction between the two structures is unclear.The BNST is a limbic forebrain structure that, in addition to the CeA, is involved in the processing and memory of emotions (13,15,20). Additionally, the anteriolateral division of the BNST (BNST AL ) serves as an extrahypothalamic conduit between the CeA and the paraventricular nucleus (PVN) of the hypothalamus, a primary brain region of the stress axis (9, 32).…”

mentioning

confidence: 99%

“…The BNST is a limbic forebrain structure that, in addition to the CeA, is involved in the processing and memory of emotions (13,15,20). Additionally, the anteriolateral division of the BNST (BNST AL ) serves as an extrahypothalamic conduit between the CeA and the paraventricular nucleus (PVN) of the hypothalamus, a primary brain region of the stress axis (9,32).…”

mentioning

confidence: 99%

The role of the anteriolateral bed nucleus of the stria terminalis in stress-induced nociception

Tran

Wiskur

Meerveld

2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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The role of the anteriolateral bed nucleus of the stria terminalis in stress-induced nociception. Am J Physiol Gastrointest Liver Physiol 302: G1301-G1309, 2012. First published April 5, 2012; doi:10.1152/ajpgi.00501.2011.-Activation of the central amygdala (CeA) by corticosterone (CORT) induces somatic and colonic hypersensitivity through corticotrophinreleasing factor (CRF)-dependent mechanisms. However, the importance of the bed nucleus of the stria terminalis (BNST), part of the extended amygdala, on nociception remains unexplored. In the present study, we test the hypothesis that stimulation of the CeA by CORT induces somatic and colonic hypersensitivity through activation of the anteriolateral BNST (BNSTAL). Animals were implanted with micropellets of CORT or cholesterol (CHOL) onto the CeA or the BNSTAL. Mechanical sensitivity was quantified using electronic von Frey filaments, and colonic nociception was measured by quantifying a visceromotor response to graded colorectal distension. In situ hybridization was used to determine mRNA levels for CRF, CRF1, and CRF2 receptors in the BNSTAL. In a second group, animals were implanted bilaterally with 1) CORT or CHOL micropellets onto the CeA; and 2) cannulas localized to the BNSTAL to administer a CRF1 receptor antagonist (CP376395). Animals implanted with CORT onto the CeA, but not the BNSTAL, exhibited increased expression of CRF mRNA and increased CRF1-to-CRF2 receptor ratio in the BNST, as well as somatic and colonic hypersensitivity compared with CHOL controls. Infusion of CP376395 into the BNSTAL inhibited somatic and colonic hypersensitivity in response to elevated amygdala CORT. Somatic and colonic hypersensitivity induced by elevated amygdala CORT is mediated via a CRF1 receptor-dependent mechanism in the BNSTAL. The CeA through a descending pathway involving the BNSTAL plays a pivotal role in somatic and colonic nociception. amygdala; bed nucleus of the stria terminalis; corticosterone; corticotrophin-releasing factor; pain IRRITABLE BOWEL SYNDROME (IBS) is a gastrointestinal (GI) disorder characterized by abdominal pain and abnormal bowel habits that are worsened during periods of stress (26). While the precise etiology and pathophysiology are unknown, clinical studies suggest that hyperactivation in brain regions involved in pain processing, including the amygdala and the bed nucleus of the stria terminalis (BNST), play an important role in IBS symtomatology (31,39). In previous preclinical studies, stereotaxic implants of corticosterone (CORT; cortisol in humans) onto the dorsal margin of the central amygdala (CeA) at pharmacological doses induced IBS-like symptoms, including anxiety-like behavior, abnormal colonic motility, and heightened somatic and colonic pain sensitivity (14,27). In the same model, elevation of amygdala CORT increased corticotrophinreleasing factor (CRF) mRNA in the CeA and the BNST (37, 38). Thus, although clinical and preclinical evidence implicates important roles of stress activation of the CeA and BNST in GI pathologies,...

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“…A stress--induced rise in corticosteroid levels modulates short--term memory, generally by promoting storage of information that is emotionally related to the stressful event, but by suppressing information that is not associated with it (Lupien and Maheu, 2007). Glucocorticoids contribute to the consolidation of contextual fear conditioning, but can also lead to memory impairments (Kolber et al, 2008;Leon--Carrion et al, 2009). The inability to remember important data worsens the individual's stress and makes the subject even more vulnerable.…”

Section: Neurological Function Of Magnesiummentioning

confidence: 99%

Magnesium in the Central Nervous System

Turner

Vink

New Perspectives in Magnesium Research

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Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning

Cited by 118 publications

References 34 publications

Persistence of fear memory across time requires the basolateral amygdala complex

Persistence of fear memory across time requires the basolateral amygdala complex

The role of the anteriolateral bed nucleus of the stria terminalis in stress-induced nociception

Magnesium in the Central Nervous System

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