Negative valence systems: sustained threat and the predatory imminence continuum

Emerging Topics in Life Sciences, Год журнала: 2022, Номер 6(5), С. 467 - 477

Опубликована: Окт. 26, 2022

This review describes the relationship between National Institute of Mental Health (U.S.A.) Research Domain Criteria (RDoC) Negative Valence System related to responses threat and Predatory Imminence Continuum model antipredator defensive behavior. While original RDoC constructs Potential Threat (anxiety) Acute (fear) fit well with pre-encounter post-encounter defense modes predatory imminence model, Sustained construct does not. Early research on bed nuclei stria terminalis (BST) suggested that when fear responding needed be sustained for a prolonged duration this region was important. However, follow-up studies indicated BST becomes critical not because but rather stimuli triggering were more difficult learn about, particularly aversive accurately predict. Instead, it is argued hippocampus act expand range conditions can trigger (Acute Threat). It further refers situations where continuum distorted causing behavior intrude into times organisms should engaging in other adaptive behaviors. Stress seen as something cause long-term disturbance state threat.

Язык: Английский

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The effect of SSRIs on fear learning: a systematic review and meta-analysis

Psychopharmacology, Год журнала: 2023, Номер 240(11), С. 2335 - 2359

Опубликована: Фев. 27, 2023

Abstract Rationale Selective serotonin reuptake inhibitors (SSRIs) are considered first-line medication for anxiety-like disorders such as panic disorder, generalized anxiety and post-traumatic stress disorder. Fear learning plays an important role in the development treatment of these disorders. Yet, effect SSRIs on fear not well known. Objective We aimed to systematically review six clinically effective acquisition, expression, extinction cued contextual conditioned fear. Methods searched Medline Embase databases, which yielded 128 articles that met inclusion criteria reported 9 human 275 animal experiments. Results Meta-analysis showed significantly reduced expression facilitated cue. Bayesian-regularized meta-regression further suggested chronic exerts a stronger anxiolytic than acute treatment. Type SSRI, species, disease-induction model, type test used did seem moderate SSRIs. The number studies was relatively small, level heterogeneity high, publication bias has likely occurred may have resulted overestimation overall sizes. Conclusions This suggests efficacy be related their effects cue, rather acquisition. However, due more general inhibition fear-related emotions. Therefore, additional meta-analyses unconditioned responses provide insight into actions

Язык: Английский

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Practitioner Review: Neurobiological consequences of childhood maltreatment – clinical and therapeutic implications for practitioners

Journal of Child Psychology and Psychiatry, Год журнала: 2023, Номер 65(3), С. 369 - 380

Опубликована: Авг. 23, 2023

Childhood maltreatment is one of the most important preventable risk factors for a wide variety psychiatric disorders. Further, when disorders emerge in maltreated individuals they typically do so at younger ages, with greater severity, more comorbid conditions, and poorer response to established treatments, resulting pernicious course an increased suicide. Practitioners treating children, adolescents, young adults will likely encounter highest prevalence clients early-onset maltreatment-associated These may be some their challenging cases.

Язык: Английский

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Nucleus Accumbens Corticotropin-Releasing Hormone Neurons Projecting to the Bed Nucleus of the Stria Terminalis Promote Wakefulness and Positive Affective State

Neuroscience Bulletin, Год журнала: 2024, Номер 40(11), С. 1602 - 1620

Опубликована: Июль 9, 2024

Abstract The nucleus accumbens (NAc) plays an important role in various emotional and motivational behaviors that rely on heightened wakefulness. However, the neural mechanisms underlying relationship between arousal emotion regulation NAc remain unclear. Here, we investigated roles of a specific subset inhibitory corticotropin-releasing hormone neurons (NAc CRH ) regulating mice. We found increased activity during wakefulness rewarding stimulation. Activation converts NREM or REM sleep to wakefulness, while inhibition these attenuates Remarkably, activation induces place preference response (PPR) decreased basal anxiety level, whereas their inactivation aversion anxious state. are identified as major projection bed stria terminalis (BNST). Furthermore, -BNST pathway similarly induced positive behaviors. Taken together, forebrain promotes associated with affective states.

Язык: Английский

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New Frontiers in Anxiety Research: The Translational Potential of the Bed Nucleus of the Stria Terminalis

Frontiers in Psychiatry, Год журнала: 2019, Номер 10

Опубликована: Июль 17, 2019

After decades of being overshadowed by the amygdala, new perspectives suggest a tiny basal forebrain region known as bed nucleus stria terminalis (BNST) may hold key insights into understanding and treating anxiety disorders. Converging research indicates that amygdala BNST play complementary but distinct functional roles during threat processing, with specializing in detection potential to maintain hypervigilance anxiety, while responds perceived presence an aversive stimulus (i.e. fear). Therefore, given human is largely driven future-oriented hypothetical threats never occur, studies involving stand at forefront essential future bring about profound for In this article, we present narrative review on BNST, summarizing its stress response, highlighting most recent advances clinical realm. Furthermore, discuss oversights current state identify avenues exploration.

Язык: Английский

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A prefrontal-bed nucleus of the stria terminalis circuit limits fear to uncertain threat

eLife, Год журнала: 2020, Номер 9

Опубликована: Дек. 15, 2020

In many cases of trauma, the same environmental stimuli that become associated with aversive events are experienced on other occasions without adverse consequence. We examined neural circuits underlying partially reinforced fear (PRF), whereby mice received tone-shock pairings half conditioning trials. Tone-elicited freezing was lower after PRF than fully (FRF) conditioning, despite an equivalent number pairings. preferentially activated medial prefrontal cortex (mPFC) and bed nucleus stria terminalis (BNST). Chemogenetic inhibition BNST-projecting mPFC neurons increased PRF, not FRF, freezing. Multiplexing chemogenetics in vivo neuronal recordings showed elevated infralimbic (IL) activity during CS onset cessation; these correlates were abolished by chemogenetic mPFC→BNST inhibition. These data suggest limit to threats a history partial association stimulus, potential implications for understanding basis trauma-related disorders.

Язык: Английский

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Limbic Neuropeptidergic Modulators of Emotion and Their Therapeutic Potential for Anxiety and Post-Traumatic Stress Disorder

Journal of Neuroscience, Год журнала: 2021, Номер 41(5), С. 901 - 910

Опубликована: Янв. 20, 2021

Post-traumatic stress disorder (PTSD) is characterized by hypervigilance, increased reactivity to unpredictable versus predictable threat signals, deficits in fear extinction, and an inability discriminate between safety. First-line pharmacotherapies for psychiatric disorders have limited therapeutic efficacy PTSD. However, recent studies advanced our understanding of the roles several limbic neuropeptides regulation defensive behaviors neural processes that are disrupted For example, preclinical shown blockers tachykinin pathways, such as Tac2 pathway, attenuate memory consolidation mice thus might unique potential early post-trauma interventions prevent PTSD development. Targeting this pathway also be beneficial regulating other symptoms PTSD, including trauma-induced aggressive behavior. In addition, clinical important role angiotensin receptors extinction promise using II receptor blockade reduce symptom severity. Additional demonstrated oxytocin foster accurate discrimination facilitating responses threats. Complementary human imaging demonstrate targets intranasal compare its with well-established anxiolytic treatments. Finally, promising data from subjects a selective vasopressin 1A antagonist reduces anxiety induced This review highlights these novel treatment core elements pathophysiology.

Язык: Английский

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Neurochemically distinct populations of the bed nucleus of stria terminalis modulate innate fear response to weak threat evoked by predator odor stimuli

Neurobiology of Stress, Год журнала: 2021, Номер 15, С. 100415 - 100415

Опубликована: Окт. 29, 2021

Anxiety and trauma-related disorders are characterized by significant alterations in threat detection, resulting inadequate fear responses evoked weak threats or safety stimuli. Recent research pointed out the important role of bed nucleus stria terminalis (BNST) anticipation modulation under ambiguous threats, hence, exaggerated may be traced back to altered BNST function. To test this hypothesis, we chemogenetically inhibited specific neuronal populations (corticotropin-releasing hormone - BNSTCRH somatostatin BNSTSST expressing neurons) a predator odor-evoked innate paradigm. The rationale for paradigm was threefold: (1) predatory cues particularly strong danger signals all vertebrate species evoking defensive on flight-avoidance-freezing dimension (conservative mechanisms), (2) odor can presented scalable manner (from strong), (3) higher-order processing olfactory information including stimuli is integrated BNST. Accordingly, exposed adult male mice low high means cat urine, low- high-dose 2-methyl-2-thiazoline (2MT), synthetic derivate fox anogenital product, which response, respectively. Then, tested impact chemogenetic inhibition neurons using crh- sst-ires-cre mouse lines. We observed that effective only conditions, reduced avoidance increased exploration source. In contrast, had no 2MT-evoked responses, but enhanced odor, representing an even weaker stimulus. These findings support notion recruited uncertain remote, potential CRH SST orchestrate complementary ways.

Язык: Английский

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Sex Differences in the Activity of Basolateral Amygdalar Neurons That Project to the Bed Nucleus of the Stria Terminalis and Their Role in Anticipatory Anxiety

Journal of Neuroscience, Год журнала: 2022, Номер 42(22), С. 4488 - 4504

Опубликована: Апрель 27, 2022

Abnormal fear and anxiety can manifest as psychiatric disorders. The bed nucleus of the stria terminalis (BNST) is implicated in sustained responding to, or anticipation of, an aversive event which be expressed anticipatory anxiety. BLA also active during sends projections to BNST. However, little known about role for neurons that project BNST (BLA-BNST) rodents. To address this, we tested whether chemogenetic inactivation BLA-BNST pathway attenuates conditioned responses produced by stimulus. For comparison, assessed social interaction, sensitive unlearned We found reduced freezing increased behaviors, but surprisingly, only males. determine sex differences neuronal activity contribute behavior, used vivo ex electrophysiological approaches. In males, projection were more excitable, coincided with a smaller after-hyperpolarization current ( I AHP ) compared other neurons; whereas females, less excitable had larger neurons. These findings demonstrate mediates anxiety-like behavior lack females this possibly because low excitability these neurons, highlights need caution when generalizing specific neurocircuits SIGNIFICANCE STATEMENT Anxiety disorders disproportionately affect women. This hints toward within neurocircuitry, yet most our understanding derived from male Furthermore, debilitating adverse events among severe symptoms, neurocircuitry. Here demonstrated required prolonged cue, Moreover, are hypoactive females. results uncover key component circuitry, cellular may explain sex-dependent circuit. Uncovering disparity provides evidence assumed basic circuitry might not readily transpose males

Язык: Английский

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A sex-specific role for the bed nucleus of the stria terminalis in proactive defensive behavior

Neuropsychopharmacology, Год журнала: 2023, Номер 48(8), С. 1234 - 1244

Опубликована: Май 4, 2023

Язык: Английский

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