scholarly journals Neuregulin-1-dependent control of amygdala microcircuits is critical for fear extinction

2021 ◽  
Author(s):  
Ming Chen ◽  
Ying Liu ◽  
Ying Li ◽  
Haibo Xu ◽  
Linlin Bi
Keyword(s):  
Anxiety Disorders ◽  
Signaling Pathway ◽  
Stress Disorder ◽  
Fear Extinction ◽  
Excitatory Input ◽  
Gabaergic Neurotransmission ◽  
Neuregulin 1 ◽  
Impaired Ability ◽  
Underlying Mechanisms ◽  
Feed Forward Inhibition

Abstract Anxiety disorders, especially posttraumatic stress disorder, are marked by an impaired ability to understand that a conditioned stimulus previously paired with a noxious stimulus is no longer noxious. Although previous studies suggest that fear extinction depends on the function of the amygdala, the underlying mechanisms are unclear. We found that NRG1 receptors (ErbB4) were abundantly expressed in the intercalated amygdala (ITC). The NRG1-ErbB4 pathway in the ITC promotes fear extinction. The NRG1-ErbB4 pathway in the ITC did not affect excitatory input to ITC neurons from BLA neurons but increased feed-forward inhibition of CeM neurons through increased GABAergic neurotransmission of ITC neurons. We also found that the NRG1-ErbB4 signaling pathway in ITC might regulate fear extinction through P/Q-type voltage-activated Ca2+ channels (VACCs) but not through L- or N-type VACCs. Overall, our results suggest that the NRG1-ErbB4 signaling pathway in the ITC might represent a potential target for the treatment of anxiety disorders.

Dispositional negativity, cognition, and anxiety disorders: An integrative translational neuroscience framework

2019 ◽  
Author(s):  
Juyoen Hur ◽  
Melissa D. Stockbridge ◽  
Andrew S. Fox ◽  
Alexander J. Shackman
Keyword(s):  
Risk Factor ◽  
Anxiety Disorders ◽  
Executive Control ◽  
Intervention Strategies ◽  
Attentional Biases ◽  
Translational Neuroscience ◽  
Adult Personality ◽  
Fundamental Dimension ◽  
To Come ◽  
Underlying Mechanisms

When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the underlying mechanisms have only recently begun to come into focus. Here, we review new insights into the nature and biological bases of dispositional negativity, a fundamental dimension of childhood temperament and adult personality and a prominent risk factor for the development of pediatric and adult anxiety disorders. Converging lines of epidemiological, neurobiological, and mechanistic evidence suggest that dispositional negativity increases the likelihood of psychopathology via specific neurocognitive mechanisms, including attentional biases to threat and deficits in executive control. Collectively, these observations provide an integrative translational framework for understanding the development and maintenance of anxiety disorders in adults and youth and set the stage for developing improved intervention strategies.

Sex Differences in Anxiety Disorders

2019 ◽  
pp. 404-432
Author(s):  
Teresa A. Piggott ◽  
Alexandra N. Duran ◽  
Isha Jalnapurkar ◽  
Tyler Kimm ◽  
Stephanie Linscheid ◽  
...  
Keyword(s):  
Sex Differences ◽  
Anxiety Disorder ◽  
Anxiety Disorders ◽  
Stress Disorder ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Considerable Research ◽  
Psychosocial Influences ◽  
Psychiatric Conditions ◽  
The Impact

Women are more likely than men to meet lifetime criteria for an anxiety disorder. Moreover, anxiety is a risk factor for the development of other psychiatric conditions, including major depression. Numerous studies have identified evidence of sex differences in anxiety disorders, and there is considerable research concerning factors that may contribute to vulnerability for anxiety in females. In addition to psychosocial influences, biological components such as the female reproductive hormone cycle have also been implicated. Although psychotropic medication is more likely to be prescribed to women, there is little controlled data available concerning sex differences in the efficacy and/or tolerability of pharmacotherapy in anxiety disorders. This chapter provides an overview of the impact of gender in the epidemiology, phenomenology, course, and treatment response in generalized anxiety disorder (GAD), social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), panic disorder (PD), and obsessive-compulsive disorder (OCD).

scholarly journals Overexpression of neuregulin 1 in GABAergic interneurons results in reversible cortical disinhibition

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yao-Yi Wang ◽  
Bing Zhao ◽  
Meng-Meng Wu ◽  
Xiao-Li Zheng ◽  
Longnian Lin ◽  
...  
Keyword(s):  
Neural Network ◽  
Intellectual Disabilities ◽  
Sodium Channel ◽  
Susceptibility Gene ◽  
Gabaergic Interneurons ◽  
Neuregulin 1 ◽  
Neuropsychiatric Diseases ◽  
Underlying Mechanisms ◽  
Gabaergic Function ◽  
Schizophrenia Susceptibility

AbstractCortical disinhibition is a common feature of several neuropsychiatric diseases such as schizophrenia, autism and intellectual disabilities. However, the underlying mechanisms are not fully understood. To mimic increased expression of Nrg1, a schizophrenia susceptibility gene in GABAergic interneurons from patients with schizophrenia, we generated gtoNrg1 mice with overexpression of Nrg1 in GABAergic interneurons. gtoNrg1 mice showed cortical disinhibition at the cellular, synaptic, neural network and behavioral levels. We revealed that the intracellular domain of NRG1 interacts with the cytoplasmic loop 1 of Nav1.1, a sodium channel critical for the excitability of GABAergic interneurons, and inhibits Nav currents. Intriguingly, activation of GABAergic interneurons or restoring NRG1 expression in adulthood could rescue the hyperactivity and impaired social novelty in gtoNrg1 mice. These results identify mechanisms underlying cortical disinhibition related to schizophrenia and raise the possibility that restoration of NRG1 signaling and GABAergic function is beneficial in certain neuropsychiatric disorders.

Neurobehavioral correlates of impaired emotion recognition in pediatric PTSD

2021 ◽  
pp. 1-11
Author(s):  
Sara A. Heyn ◽  
Collin Schmit ◽  
Taylor J. Keding ◽  
Richard Wolf ◽  
Ryan J. Herringa
Keyword(s):  
Emotion Recognition ◽  
Stress Disorder ◽  
Recognition Task ◽  
Typically Developing ◽  
Biological Mechanisms ◽  
Impaired Ability ◽  
Multimethod Approach ◽  
Threat Recognition ◽  
Neurological Substrates

Abstract Despite broad evidence suggesting that adversity-exposed youth experience an impaired ability to recognize emotion in others, the underlying biological mechanisms remains elusive. This study uses a multimethod approach to target the neurological substrates of this phenomenon in a well-phenotyped sample of youth meeting diagnostic criteria for posttraumatic stress disorder (PTSD). Twenty-one PTSD-afflicted youth and 23 typically developing (TD) controls completed clinical interview schedules, an emotion recognition task with eye-tracking, and an implicit emotion processing task during functional magnetic resonance imaging )fMRI). PTSD was associated with decreased accuracy in identification of angry, disgust, and neutral faces as compared to TD youth. Of note, these impairments occurred despite the normal deployment of visual attention in youth with PTSD relative to TD youth. Correlation with a related fMRI task revealed a group by accuracy interaction for amygdala–hippocampus functional connectivity (FC) for angry expressions, where TD youth showed a positive relationship between anger accuracy and amygdala–hippocampus FC; this relationship was reversed in youth with PTSD. These findings are a novel characterization of impaired threat recognition within a well-phenotyped population of severe pediatric PTSD. Further, the differential amygdala–hippocampus FC identified in youth with PTSD may imply aberrant efficiency of emotional contextualization circuits.

scholarly journals MiRNA-143 mediates the proliferative signaling pathway of FSH and regulates estradiol production

2017 ◽  
Vol 234 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Li Zhang ◽  
XiaoXin Zhang ◽  
Xuejing Zhang ◽  
Yu Lu ◽  
Lei Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Loss Of Function ◽  
Cellular Processes ◽  
Cell Functions ◽  
Genes Expression ◽  
Underlying Mechanisms

MicroRNAs (MiRNAs) play important regulatory roles in many cellular processes. MiR-143 is highly enriched in the mouse ovary, but its roles and underlying mechanisms are not well understood. In the current study, we show that miR-143 is located in granulosa cells of primary, secondary and antral follicles. To explore the specific functions of miR-143, we transfected miR-143 inhibitor into primary cultured granulosa cells to study the loss of function of miR-143 and the results showed that miR-143 silencing significantly increased estradiol production and steroidogenesis-related gene expression. Moreover, our in vivo and in vitro studies showed that follicular stimulating hormone (FSH) significantly decreased miR-143 expression. This function of miR-143 is accomplished by its binding to the 3’-UTR of KRAS mRNA. Furthermore, our results demonstrated that miR-143 acts as a negative regulating molecule mediating the signaling pathway of FSH and affecting estradiol production by targeting KRAS. MiR-143 also negatively acts in regulating granulosa cells proliferation and cell cycle-related genes expression. These findings indicate that miR-143 plays vital roles in FSH-induced estradiol production and granulosa cell proliferation, providing a novel mechanism that involves miRNA in regulating granulosa cell functions.

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