Prepronociceptin-Expressing Neurons in the Extended Amygdala Encode and Promote Rapid Arousal Responses to Motivationally Salient Stimuli DOI Creative Commons
Jose Rodríguez-Romaguera, Randall L. Ung, Hiroshi Nomura

et al.

Cell Reports, Journal Year: 2020, Volume and Issue: 33(6), P. 108362 - 108362

Published: Nov. 1, 2020

Motivational states consist of cognitive, emotional, and physiological components controlled by multiple brain regions. An integral component this neural circuitry is the bed nucleus stria terminalis (BNST). Here, we identify that neurons within BNST express gene prepronociceptin (PnocBNST) modulate rapid changes in arousal occur upon exposure to motivationally salient stimuli. Using vivo two-photon calcium imaging, find PnocBNST neuronal responses directly correspond with increases pupillary size when mice are exposed aversive rewarding odors. Furthermore, optogenetic activation these anxiety-like behaviors but does not induce approach, avoidance, or locomotion. These findings suggest excitatory encode anxiety states. Further histological, electrophysiological, single-cell RNA sequencing data reveal composed genetically anatomically identifiable subpopulations may differentially tune motivational

Language: Английский

Bed nucleus of the stria terminalis regulates fear to unpredictable threat signals DOI Creative Commons
Travis D. Goode, Reed L. Ressler,

Gillian M. Acca

et al.

eLife, Journal Year: 2019, Volume and Issue: 8

Published: April 4, 2019

The bed nucleus of the stria terminalis (BNST) has been implicated in conditioned fear and anxiety, but specific factors that engage BNST defensive behaviors are unclear. Here we examined whether mediates freezing to stimuli (CSs) poorly predict onset aversive unconditioned (USs) rats. Reversible inactivation selectively reduced CSs signaled US (e.g., a backward CS followed US), did not eliminate forward even when they predicted USs variable intensity. Additionally, (but forward) increased Fos ventral BNST-projecting neurons infralimbic region medial prefrontal cortex (mPFC), hippocampus or amygdala. These data reveal circuits regulate unpredictable threats, which may be critical etiology expression anxiety.

Language: Английский

Citations

108
Sex differences in fear extinction DOI
Eric Raúl Velasco, Antonio Florido, Mohammed R. Milad

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2019, Volume and Issue: 103, P. 81 - 108

Published: May 23, 2019

Language: Английский

Citations

104
Optogenetic silencing of a corticotropin-releasing factor pathway from the central amygdala to the bed nucleus of the stria terminalis disrupts sustained fear DOI
Arun Asok,

A. J. Draper,

Alexander F. Hoffman

et al.

Molecular Psychiatry, Journal Year: 2017, Volume and Issue: 23(4), P. 914 - 922

Published: April 25, 2017

Language: Английский

Citations

101
Anxiety and the Neurobiology of Temporally Uncertain Threat Anticipation DOI Creative Commons
Juyoen Hur,

Jason F. Smith,

Kathryn A. DeYoung

et al.

Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 40(41), P. 7949 - 7964

Published: Sept. 21, 2020

When extreme, anxiety—a state of distress and arousal prototypically evoked by uncertain danger—can be debilitating. Uncertain anticipation is a shared feature situations that elicit signs symptoms anxiety across psychiatric disorders, species, assays. Despite the profound significance for human health wellbeing, neurobiology uncertain-threat remains unsettled. Leveraging paradigm adapted from animal research optimized fMRI signal decomposition, we examined neural circuits engaged during temporally certain threat in 99 men women. Results revealed systems recruited are anatomically colocalized frontocortical regions, extended amygdala, periaqueductal gray. Comparison conditions demonstrated this circuitry can fractionated, with regions showing relatively stronger engagement threat, amygdala reverse pattern. Although there widespread agreement bed nucleus stria terminalis dorsal amygdala—the two major subdivisions amygdala—play critical role orchestrating adaptive responses to potential danger, their precise contributions have remained contentious. Follow-up analyses these show statistically indistinguishable anticipation. These observations provide framework conceptualizing fear, understanding functional neuroanatomy humans, accelerating development more effective intervention strategies pathological anxiety. SIGNIFICANCE STATEMENT Anxiety—an emotion associated harm—has public health, yet underlying unclear. novel neuroimaging large sample, identify core circuit responsive both anticipation, fractionated into bias one kind or other. The occupies center stage neuropsychiatric models anxiety, but its architecture has Here demonstrate threat. Collectively, indicate need revise how think about fear.

Language: Английский

Citations

99
How Human Amygdala and Bed Nucleus of the Stria Terminalis May Drive Distinct Defensive Responses DOI Creative Commons
Floris Klumpers, Marijn C. W. Kroes, Johanna M.P. Baas

et al.

Journal of Neuroscience, Journal Year: 2017, Volume and Issue: 37(40), P. 9645 - 9656

Published: Sept. 11, 2017

The ability to adaptively regulate responses the proximity of potential danger is critical survival and imbalance in this system may contribute psychopathology. bed nucleus stria terminalis (BNST) implicated defensive responding during uncertain threat anticipation whereas amygdala drive upon more acute danger. This functional dissociation between BNST however controversial, human evidence scarce. Here we used data from two independent magnetic resonance imaging studies [ n = 108 males 70 (45 females)] probe how coordination shock actual confrontation. In a subset participants Sample 2 ( 48) demonstrate that confrontation evoke bradycardic tachycardic responses, respectively. Further, show each sample when going moment neural activity shifted region anatomically consistent with toward amygdala. Comparisons connectivity processing showed overlapping yet also consistently divergent profiles for Finally, childhood maltreatment levels predicted amygdala, but not BNST, hyperactivity anticipation. Our results support an evolutionary conserved, distance-dependent dynamic balance activity. Shifts enable shifts reactions via demonstrated differential connectivity. indicate early life stress tip route predispose affective disorder. SIGNIFICANCE STATEMENT Previously proposed contributions fear anxiety have been recently debated. Despite significance understanding their reactions, there paucity directly compared these regions on processing. We strong dissociable role by demonstrating large participant samples they distinct temporal signature as well discriminable pattern connections sensitivity threat.

Language: Английский

Citations

98
Acute engagement of Gq-mediated signaling in the bed nucleus of the stria terminalis induces anxiety-like behavior DOI

Christopher M. Mazzone,

Dipanwita Pati, Michael Michaelides

et al.

Molecular Psychiatry, Journal Year: 2016, Volume and Issue: 23(1), P. 143 - 153

Published: Dec. 13, 2016

Language: Английский

Citations

87
Dispositional negativity, cognition, and anxiety disorders: An integrative translational neuroscience framework DOI
Juyoen Hur, Melissa D. Stockbridge, Andrew S. Fox

et al.

Progress in brain research, Journal Year: 2019, Volume and Issue: unknown, P. 375 - 436

Published: Jan. 1, 2019

Language: Английский

Citations

84
Role of oxytocin in the control of stress and food intake DOI Creative Commons
Tatsushi Onaka, Yuki Takayanagi

Journal of Neuroendocrinology, Journal Year: 2019, Volume and Issue: 31(3)

Published: Feb. 20, 2019

Oxytocin neurones in the hypothalamus are activated by stressful stimuli and food intake. The oxytocin receptor is located various brain regions, including sensory information‐processing cerebral cortex; cognitive prefrontal reward‐related regions such as ventral tegmental areas, nucleus accumbens raphe nucleus; stress‐related areas amygdala, hippocampus, ventrolateral part of ventromedial periaqueductal gray; homeostasis‐controlling hypothalamus; dorsal motor complex controlling intestinal functions. affects behavioural neuroendocrine stress responses terminates intake acting on metabolic or nutritional homeostasis system, modulating emotional processing, reducing reward values intake, facilitating processing via multiple regions. also plays a role interactive actions between contributes to adaptive active coping behaviours.

Language: Английский

Citations

80
Intrinsic functional connectivity of the central extended amygdala DOI Open Access
Rachael M. Tillman, Melissa D. Stockbridge,

Brendon M. Nacewicz

et al.

Human Brain Mapping, Journal Year: 2017, Volume and Issue: 39(3), P. 1291 - 1312

Published: Dec. 12, 2017

The central extended amygdala (EAc)-including the bed nucleus of stria terminalis (BST) and (Ce)-plays a critical role in triggering fear anxiety is implicated development range debilitating neuropsychiatric disorders. Although it widely believed that these disorders reflect coordinated activity distributed neural circuits, functional architecture EAc network degree to which BST Ce show distinct patterns connectivity unclear. Here, we used novel combination imaging approaches trace 130 healthy, racially diverse, community-dwelling adults. Multiband imaging, high-precision registration techniques, spatially unsmoothed data maximized anatomical specificity. Using newly developed seed regions, whole-brain regression analyses revealed robust between via sublenticular amygdala, ribbon subcortical gray matter encompassing ventral amygdalofugal pathway. Both regions displayed coupling with ventromedial prefrontal cortex (vmPFC), midcingulate (MCC), insula, anterior hippocampus. showed stronger thalamus, striatum, periaqueductal gray, several territories. only showing were neighboring dorsal amygdalohippocampal area, These observations provide baseline against compare special populations, inform our understanding normal pathological anxiety, showcase image techniques are likely be useful for researchers working "deidentified" neuroimaging data.

Language: Английский

Citations

80
Common neurocircuitry mediating drug and fear relapse in preclinical models DOI Creative Commons
Travis D. Goode, Stephen Maren

Psychopharmacology, Journal Year: 2018, Volume and Issue: 236(1), P. 415 - 437

Published: Sept. 25, 2018

Comorbidity of anxiety disorders, stressor- and trauma-related substance use disorders is extremely common. Moreover, therapies that reduce pathological fear on the one hand, drug-seeking other, often prove short-lived are susceptible to relapse. Considerable advances have been made in study neurobiology both aversive appetitive extinction, this work reveals shared neural circuits contribute suppression relapse conditioned responses associated with trauma or drug use.The goal review identify common mechanisms underlying across domains addiction biology learning preclinical animal models. We focus primarily engaged during expression relapse.After brain involving medial prefrontal cortex hippocampus come regulate by amygdala, bed nucleus stria terminalis, accumbens. During relapse, hippocampal projections inhibit retrieval extinction memories resulting a loss inhibitory control over fear- drug-associated conditional responding.The overlapping systems for may explain co-occurrence behaviors.

Language: Английский

Citations

68