Abstract

The bed nuclei of the stria terminalis (BST) is a limbic region in the extended amygdala that is heavily implicated in anxiety processing and hypothalamic-adrenal-pituitary (HPA) axis activation. The BST is complex, with many nuclei expressing different neurotransmitters and receptors involved in a variety of signaling pathways. One neurotransmitter that helps link its functions is corticotropin releasing hormone (CRH). BST CRH neuron activation may cause both anxiogenic and anxiolytic effects in rodents, and CRH neurons interact with other neuron types to influence anxiety-like responses as well as alcohol and drug–seeking behavior. This review covers the link between BST CRH neurons and thirteen other neurotransmitters and receptors and analyzes their effect on rodent behavior. Additionally, it covers the translational potential of targeting CRH signaling pathways for the treatment of human mental health disorders. Given the massive impact of anxiety, mood, and substance use disorders on our society, further research into BST CRH signaling is critical to alleviate the social and economic burdens of those disorders.

Highlights

  • One in three people in the United States will develop an anxiety disorder during their lifetime (Craske et al, 2017)

  • The bed nuclei of the stria terminalis (BST) serves as a hub for the regulation of chronic fear responses and other behaviors that can lead to anxiety and mood disorders

  • In the BSTa, changes to corticotropin releasing hormone (CRH) signaling are critical for these effects

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Summary

INTRODUCTION

One in three people in the United States will develop an anxiety disorder during their lifetime (Craske et al, 2017). The BST is involved in the development of other maladaptive behaviors beyond anxiety disorders It has been implicated in binge drinking and alcohol use disorders (AUDs), the stress-induced reinstatement of drug-seeking behaviors (Silberman and Winder, 2013; Nentwig et al, 2019; Snyder et al, 2019). In this model of the addiction cycle, withdrawal produces negative affect and dysregulated BST CRH signaling.

BST NOMENCLATURE AND ANATOMY
OVERVIEW OF CRH SIGNALING IN THE BST
DA eCB
ARGININE VASOPRESSIN
NEUROPEPTIDE S
PROTEIN KINASE C DELTA
NEUROPEPTIDE Y
Current Applications in Deep Brain Stimulation Therapy in Humans
Findings
CONCLUSION AND FUTURE DIRECTIONS
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