The Neurobiology of Dispositional Negativity and Attentional Biases to Threat: Implications for Understanding Anxiety Disorders in Adults and Youth

Journal of Experimental Psychopathology, Journal Year: 2016, Volume and Issue: 7(3), P. 311 - 342

Published: June 26, 2016

When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the neurocognitive mechanisms that confer increased risk have only recently begun come into focus. Here we review recent work highlighting importance of neural circuits centered on amygdala. We begin by describing dispositional negativity, a core dimension childhood temperament adult personality an important factor for development disorders other kinds stress-sensitive psychopathology. Converging lines epidemiological, neurophysiological, mechanistic evidence indicate amygdala supports stable individual differences negativity across lifespan contributes etiology adults youth. Hyper-vigilance attentional biases threat prominent features anxious phenotype there is growing they contribute Anatomical studies show hub, poised govern attention via projections sensory cortex ascending neuromodulatory systems. Imaging lesion demonstrate plays key role selecting prioritizing processing threat-related cues. Collectively, these observations provide neurobiologically-grounded framework understanding maintenance youth set stage developing improved intervention strategies.

Language: Английский

---

Targeting Corticotropin-Releasing Factor Projections from the Oval Nucleus of the Bed Nucleus of the Stria Terminalis Using Cell-Type Specific Neuronal Tracing Studies in Mouse and Rat Brain

Journal of Neuroendocrinology, Journal Year: 2016, Volume and Issue: 28(12)

Published: Dec. 1, 2016

The bed nucleus of the stria terminalis (BNST) is known to play a critical role in mediating behavioural and autonomic responses stressors. oval BNST (BNSTov) contains cell bodies that synthesise stress hormone corticotropin-releasing factor (CRF). Although afferent fibres originating from BNSTov have been shown innervate several key structures neuroendocrine central system, question remains as whether some these are CRF-positive. To directly address this question, we injected 'floxed' anterograde tracer (rAAV5/EF1a-DIO-mCherry) into CRFp3.0CreGFP transgenic mice, which express green fluorescent protein (GFP) under control CRF promoter. Serial sections were then analysed for presence double-labelled potential projection sites. determine neurons rat send comparable projections, infused with an adeno-associated viral vector (AAV) human synapsin promoter drives enhanced GFP expression. We used immunoreactivity examine axon terminals sites brain AAV-infused rats. observed terminal fields mouse Dorsal raphe (DRD), paraventricular hypothalamus and, lesser extent, ventral tegmental area. found boutons accumbens shell, prelimbic cortex posterior basolateral amygdala. most intense double-labelling was midbrain, including substantia nigra pars compacta, red nucleus, periaqueductal grey pontine nuclei, well DRD. results present study indicate output they projections not only centres regulation, but also regions modulating reward motivation, vigilance motor function, affective behaviour.

Language: Английский

---

c-Fos mapping of brain regions activated by multi-modal and electric foot shock stress

Neurobiology of Stress, Journal Year: 2018, Volume and Issue: 8, P. 92 - 102

Published: Feb. 1, 2018

Real-world stressors are complex and multimodal, involving physical, psychological, social dimensions. However, the brain networks that mediate stress responses to these stimuli need be further studied. We used c-Fos mapping in mice characterize circuits activated by exposure a single episode of multimodal (MMS), compared electric foot shocks (EFS). focused on characterizing activity stress-relevant regions including paraventricular nucleus (PVN) hypothalamus bed stria terminalis (BNST). also assessed stress-induced activation CRH-positive neurons each structures. MMS EFS an overlapping network with similar time course. expression within PVN BNST peaked 30-60 min after both EFS, returned baseline levels 24 h. Quantification subregions revealed while all exposure, neuronal density was significantly higher dorsomedial ventral relative dorsolateral BNST. Our preliminary assessment indicated great majority or EFS-activated were (>87%); contrast, about 6-35% CRH-positive. findings indicate effective at activating areas support use as approach for studying multidimensional animal models. The results reveal part common neural circuit substrate involved processing related stress.

Language: Английский

---

Oxytocin facilitates adaptive fear and attenuates anxiety responses in animal models and human studies—potential interaction with the corticotropin-releasing factor (CRF) system in the bed nucleus of the stria terminalis (BNST)

Cell and Tissue Research, Journal Year: 2018, Volume and Issue: 375(1), P. 143 - 172

Published: July 28, 2018

Language: Английский

---

The Parental Brain

Oxford University Press eBooks, Journal Year: 2020, Volume and Issue: unknown

Published: July 1, 2020

Abstract The Parental Brain: Mechanisms, Development, and Evolution takes a three-pronged approach to the parental brain. first part of book deals with neural mechanisms. Subcortical circuits are crucially involved in behavior, and, for most mammals, physiological events pregnancy parturition prime these so that they become responsive infant stimuli, allowing onset maternal behavior at parturition. However, since paternal alloparental occur some mammalian species, alternate mechanisms shown exist regulate access stimuli circuits. In humans, cortical interact subcortical feeling states (emotions) cognitions can be translated into behavior. section on development emphasizes experiential basis intergenerational continuity normal abnormal animals humans: way mother treats her affects infant’s brain subsequent Genetic factors, including epigenetic processes gene by environment (G × E) interactions, also involved. chapter evolution presents evidence likely provided foundation or template other strong prosocial bonds. particular, have probably been utilized natural selection promote hyper-cooperation hyper-prosociality human social groups. A unique aspect this is its integration animal research create complete understanding

Language: Английский

---

Chronic Stress Induces Maladaptive Behaviors by Activating Corticotropin-Releasing Hormone Signaling in the Mouse Oval Bed Nucleus of the Stria Terminalis

Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 40(12), P. 2519 - 2537

Published: Feb. 13, 2020

The bed nucleus of the stria terminalis (BNST) is a forebrain region highly responsive to stress that expresses corticotropin-releasing hormone (CRH) and implicated in mood disorders, such as anxiety. However, exact mechanism by which chronic induces CRH-mediated dysfunction BNST maladaptive behaviors remains unclear. Here, we first confirmed selective acute optogenetic activation oval (ovBNST) increases avoidance male mice. Next, found 6 week variable mild (CVMS) paradigm resulted increased cellular excitability ovBNST CRH neurons potentiating mEPSC amplitude, altering resting membrane potential, diminishing M-currents (a voltage-gated K + current stabilizes potential) ex vivo slices. CVMS also c-fos cells following handling. We next investigated potential molecular underlying electrophysiological effects observed pituitary adenylate cyclase-activating polypeptide (PACAP; upstream regulator) but decreased striatal-enriched protein tyrosine phosphatase STEP inhibitor) ovBNST. Interestingly, were reversed CRHR1-selective antagonist R121919 application. activated kinase A (PKA) BNST, infusion PKA-selective H89 into CVMS. Coadministration PKA agonist forskolin prevented beneficial R121919. Finally, induced an increase surface expression phosphorylated GluR1 (S845) BNST. Collectively, these findings highlight novel indispensable stress-induced role for PKA-dependent CRHR1 signaling activating mediating behaviors. SIGNIFICANCE STATEMENT Chronic rodents. precise mechanisms remain demonstrate activates (CRH)-associated amplitude decreasing M-current These alterations mediated A-dependent signaling. Our results thus importance disorders.

Language: Английский

---

Neuronal diversity of the amygdala and the bed nucleus of the stria terminalis

Handbook of behavioral neuroscience, Journal Year: 2020, Volume and Issue: unknown, P. 63 - 100

Published: Jan. 1, 2020

Language: Английский

---

Extended amygdala-parabrachial circuits alter threat assessment and regulate feeding

Science Advances, Journal Year: 2021, Volume and Issue: 7(9)

Published: Feb. 26, 2021

Circuit dissection techniques reveal that extended amygdala-brainstem circuitry integrates threat and feeding behavior.

Language: Английский

---

Neuroendocrine control of appetite and metabolism

Experimental & Molecular Medicine, Journal Year: 2021, Volume and Issue: 53(4), P. 505 - 516

Published: April 1, 2021

Abstract Body homeostasis is predominantly controlled by hormones secreted endocrine organs. The central nervous system contains several important structures, including the hypothalamic-pituitary axis. Conventionally, neurohormones released hypothalamus and pituitary gland (hypophysis) have received much attention owing to unique functions of end their target peripheral organs (e.g., glucocorticoids adrenal glands). Recent advances in mouse genetics revealed metabolic hypothalamic neurohormone-expressing cells, many which are not readily explained action corresponding classical downstream hormones. Notably, newly identified better conventional neurotransmitters glutamate GABA) that constitute a neuronal circuit. In this review, we discuss regulation appetite metabolism with focus on distinct contributions these neurons.

Language: Английский

---

Peptidergic and functional delineation of the Edinger-Westphal nucleus

Cell Reports, Journal Year: 2023, Volume and Issue: 42(8), P. 112992 - 112992

Published: Aug. 1, 2023

Many neuronal populations that release fast-acting excitatory and inhibitory neurotransmitters in the brain also contain slower-acting neuropeptides. These facultative peptidergic cell types are common, but it remains uncertain whether neurons solely peptides exist. Our fluorescence situ hybridization, genetically targeted electron microscopy, electrophysiological characterization suggest most of non-cholinergic, centrally projecting Edinger-Westphal nucleus mice obligately peptidergic. We further show, using anterograde projection mapping, monosynaptic retrograde tracing, angled-tip fiber photometry, chemogenetic modulation ablation conjunction with canonical assays for anxiety, this population activates response to loss motor control promotes anxiety responses. Together, these findings elucidate an integrative, ethologically relevant role functionally align periaqueductal gray, where resides. This work advances our understanding provides a framework future investigations systems.

Language: Английский

---