Contributions of the Central Extended Amygdala to Fear and Anxiety

Journal of Neuroscience, Journal Year: 2016, Volume and Issue: 36(31), P. 8050 - 8063

Published: Aug. 3, 2016

It is widely thought that phasic and sustained responses to threat reflect dissociable circuits centered on the central nucleus of amygdala (Ce) bed stria terminalis (BST), two major subdivisions extended amygdala. Early versions this hypothesis remain highly influential have been incorporated into National Institute Mental Health Research Domain Criteria framework. However, new observations encourage a different perspective. Anatomical studies show Ce BST form tightly interconnected unit, where kinds threat-relevant information can be integrated used assemble states fear anxiety. Imaging in humans monkeys exhibit similar functional profiles. Both regions are sensitive range aversive challenges, including uncertain or temporally remote threat; both covary with concurrent signs symptoms anxiety; short-lived heightened activity during exposure diffusely threatening contexts. Mechanistic demonstrate control expression anxiety diffuse threat. These compel reconsideration amygdala9s contributions its role neuropsychiatric disease.

Language: Английский

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Dispositional negativity: An integrative psychological and neurobiological perspective.

Psychological Bulletin, Journal Year: 2016, Volume and Issue: 142(12), P. 1275 - 1314

Published: Oct. 11, 2016

Dispositional negativity-the propensity to experience and express more frequent, intense, or enduring negative affect-is a fundamental dimension of childhood temperament adult personality. Elevated levels dispositional negativity can have profound consequences for health, wealth, happiness, drawing the attention clinicians, researchers, policymakers. Here, we highlight recent advances in our understanding psychological neurobiological processes linking stable individual differences momentary emotional states. Self-report data suggest that 3 key pathways-increased stressor reactivity, tonic increases affect, increased exposure-explain most heightened affect characterizes individuals with disposition. Of these pathways, tonically elevated, indiscriminate appears be central daily life relevant development psychopathology. New behavioral biological provide insights into neural systems underlying pathways motivate hypothesis seemingly "tonic" may actually reflect reactivity stressors are remote, uncertain, diffuse. Research focused on humans, monkeys, rodents suggests this reflects trait-like variation activity connectivity several brain regions, including extended amygdala parts prefrontal cortex. Collectively, observations an integrative psychobiological framework dynamic cascade bind traits states and, ultimately, disorders other kinds adverse outcomes. (PsycINFO Database Record

Language: Английский

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The central extended amygdala in fear and anxiety: Closing the gap between mechanistic and neuroimaging research

Neuroscience Letters, Journal Year: 2017, Volume and Issue: 693, P. 58 - 67

Published: Nov. 30, 2017

Language: Английский

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Amygdala Circuit Substrates for Stress Adaptation and Adversity

Biological Psychiatry, Journal Year: 2021, Volume and Issue: 89(9), P. 847 - 856

Published: Jan. 8, 2021

Brain systems that promote maintenance of homeostasis in the face stress have significant adaptive value. A growing body work across species demonstrates a critical role for amygdala promoting by regulating physiological and behavioral responses to stress. This review focuses on an emerging evidence has begun delineate contribution specific long-range circuits mediating effects After summarizing major anatomical features its connectivity other limbic structures, we discuss recent findings from rodents showing how causes structural functional remodeling neuronal outputs defined cortical subcortical target regions. We also consider some environmental genetic factors been found moderate responds relate preclinical literature current understanding pathophysiology treatment stress-related neuropsychiatric disorders. Future effort translate these clinics may help develop valuable tools prevention, diagnosis, diseases.

Language: Английский

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The Anterior Insular Cortex→Central Amygdala Glutamatergic Pathway Is Critical to Relapse after Contingency Management

Neuron, Journal Year: 2017, Volume and Issue: 96(2), P. 414 - 427.e8

Published: Oct. 1, 2017

Despite decades of research on neurobiological mechanisms psychostimulant addiction, the only effective treatment for many addicts is contingency management, a behavioral that uses alternative non-drug reward to maintain abstinence. However, when management discontinued, most relapse drug use. The brain underlying after cessation are largely unknown, and, until recently, an animal model this human condition did not exist. Here we used novel rat model, in which availability mutually exclusive palatable food maintains prolonged voluntary abstinence from intravenous methamphetamine self-administration, demonstrate activation monosynaptic glutamatergic projections anterior insular cortex central amygdala critical management. We identified cortex-to-central projection as new addiction- and motivation-related potential target prevention.

Language: Английский

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A Central Extended Amygdala Circuit That Modulates Anxiety

Journal of Neuroscience, Journal Year: 2018, Volume and Issue: 38(24), P. 5567 - 5583

Published: May 21, 2018

Both the amygdala and bed nucleus of stria terminalis (BNST) have been implicated in maladaptive anxiety characteristics disorders. However, underlying circuit cellular mechanisms remained elusive. Here we show that mice with Erbb4 gene deficiency somatostatin-expressing (SOM+) neurons exhibit heightened as measured elevated plus maze test open field test, two assays commonly used to assess anxiety-related behaviors rodents. Using a combination electrophysiological, molecular, genetic, pharmacological techniques, demonstrate abnormal mutant is caused by enhanced excitatory synaptic inputs onto SOM+ central (CeA), resulting reduction inhibition downstream BNST. Notably, our results indicate an increase dynorphin signaling CeA mediates paradoxical BNST neurons, consequent activity both necessary for sufficient drive anxiety. Finally, associated dysfunctions increased CeA-BNST can be recapitulated stress wild-type mice. Together, unravel previously unknown processes extended cause anxiety.SIGNIFICANCE STATEMENT The has behaviors, but are unclear. found (CeA) controls through modulation terminalis, process mediated CeA. Our reveal may account

Language: Английский

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Role of the bed nucleus of the stria terminalis in aversive learning and memory

Learning & Memory, Journal Year: 2017, Volume and Issue: 24(9), P. 480 - 491

Published: Aug. 16, 2017

Surviving threats in the environment requires brain circuits for detecting (or anticipating) danger and coordinating appropriate defensive responses (e.g., increased cardiac output, stress hormone release, freezing behavior). The bed nucleus of stria terminalis (BNST) is a critical interface between "affective forebrain"-including amygdala, ventral hippocampus, medial prefrontal cortex-and hypothalamic brainstem areas that have been implicated neuroendocrine, autonomic, behavioral to actual or anticipated threats. However, precise contribution BNST behavior unclear, both terms antecedent stimuli mobilize activity consequent reactions. For example, it well known essential contextual fear conditioning, but dispensable conditioning discrete conditioned (CSs), at least as indexed by behavior. recent evidence suggests there are circumstances which may persist independent BNST. Furthermore, involved reinstatement relapse) extinguished CSs. As such, gaps understanding how contributes fundamental processes Pavlovian conditioning. Here, we attempt provide an integrative account function We discuss distinctions unconditioned role organizing behaviors associated with these states. propose mediates responses-not based on modality duration threat response threat-but rather consequence ability stimulus predict when aversive outcome will occur (i.e., its temporal predictability). argue not uniquely mobilized sustained responses. In contrast, poorly

Language: Английский

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A Corticotropin Releasing Factor Network in the Extended Amygdala for Anxiety

Journal of Neuroscience, Journal Year: 2018, Volume and Issue: 39(6), P. 1030 - 1043

Published: Dec. 10, 2018

The central amygdala (CeA) is important for fear responses to discrete cues. Recent findings indicate that the CeA also contributes states of sustained apprehension characterize anxiety, although little known about neural circuitry involved. stress neuropeptide corticotropin releasing factor (CRF) anxiogenic and produced by subpopulations neurons in lateral dorsolateral bed nucleus stria terminalis (dlBST). Here we investigated function these CRF stress-induced anxiety using chemogenetics male rats express Cre recombinase from a Crh promoter. Anxiety-like behavior was mediated projections dlBST depended on activation CRF1 receptors within dlBST. Our identify →CRF circuit generating anxiety-like provide mechanistic support recent human primate data suggesting BST act together generate anxiety. SIGNIFICANCE STATEMENT Anxiety negative emotional state critical survival, but persistent, exaggerated causes substantial morbidity. Identifying brain regions neurotransmitter systems drive can help developing effective treatment. Much evidence rodents indicates (BST) behaviors, more implicate CeA. neuronal are currently subjects intense investigation. show release corticotropin-releasing behaviors via pathway dorsal activates local neurons. Thus, our CeA→BST generates behavior.

Language: Английский

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Functional Connectivity within the Primate Extended Amygdala Is Heritable and Associated with Early-Life Anxious Temperament

Journal of Neuroscience, Journal Year: 2018, Volume and Issue: 38(35), P. 7611 - 7621

Published: July 30, 2018

Children with an extremely inhibited, anxious temperament (AT) are at increased risk for anxiety disorders and depression. Using a rhesus monkey model of early-life AT, we previously demonstrated that metabolism in the central extended amygdala (EAc), including nucleus (Ce) bed stria terminalis (BST), is associated trait-like variation AT. Here, use fMRI to examine relationships between Ce–BST functional connectivity AT large multigenerational family pedigree monkeys (n = 170 females 208 males). Results demonstrate heritable, accounts significant but modest portion variance coheritable Interestingly, AT-related BST were not correlated accounted non-overlapping Exploratory analyses suggest hypothalamus periaqueductal gray. Together, these results importance coordinated function within EAc determining individual differences brain regions its behavioral neuroendocrine components. SIGNIFICANCE STATEMENT Anxiety directly impact lives nearly one five people, accounting substantial worldwide suffering disability. nonhuman primate understand neurobiology underlying develop disorders. Leveraging same kinds neuroimaging measures routinely used human studies, activation with, coinherited Understanding how work together produce extreme provides neural target interventions promise preventing lifelong disability at-risk children.

Language: Английский

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Brain mechanisms of HPA axis regulation: neurocircuitry and feedback in context Richard Kvetnansky lecture

Stress, Journal Year: 2020, Volume and Issue: 23(6), P. 617 - 632

Published: Nov. 1, 2020

Regulation of stress reactivity is a fundamental priority all organisms. Stress responses are critical for survival, yet can also cause physical and psychological damage. This review provides synopsis brain mechanisms designed to control physiological stress, focusing primarily on glucocorticoid secretion via the hypothalamo-pituitary-adrenocortical (HPA) axis. The literature strong support multi-faceted HPA axis responses, involving both direct indirect actions at paraventricular nucleus (PVN) corticotropin releasing hormone neurons driving secretory cascade. PVN directly excited by afferents from brainstem hypothalamic circuits, likely relaying information homeostatic challenge. Amygdala subnuclei drive indirectly disinhibition, mediated GABAergic relays onto PVN-projecting in hypothalamus bed stria terminalis (BST). Inhibition stressor-evoked an elaborate network receptor (GR)-containing providing distributed negative feedback signal that inhibits neurons. Prefrontal hippocampal play major role inhibition, again BST PVN. complexity regulatory process suggests stressors integrated across functional disparate circuits prior accessing PVN, with regions such as prime position relay contextual provided these sources into appropriate activation. Dysregulation disease product inappropriate checks balances between excitatory inhibitory inputs ultimately impacting output.

Language: Английский

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