Danger and distress: Parabrachial-extended amygdala circuits. (15th October 2021)

• Record Type: Journal Article
• Authors: Jaramillo, A.A.; Brown, J.A.; Winder, D.G.
• Is Part Of: Neuropharmacology. Volume 198(2021)
• Publication Date: 2021-10-15
• Subjects: Stress -- Anxiety -- Negative affect -- Fear -- Hyperkatifea; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2021.108757
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Our understanding of the role of the parabrachial nucleus (PBN) has evolved as technology has advanced, in part due to cell-specific studies and complex behavioral assays. This is reflected in the heterogeneous neuronal populations within the PBN to the extended amygdala (EA) circuits which encompass the bed nucleus of the stria terminalis (BNST) and central amygdala (CeA) circuitry, as they differentially modulate aspects of behavior in response to diverse threat-like contexts necessary for survival. Here we review how the PBN→CeA and PBN→BNST pathways differentially modulate fear-like behavior, innate and conditioned, through unique changes in neurotransmission in response to stress-inducing contexts. Furthermore, we hypothesize how in specific instances the PBN→CeA and PBN→BNST circuits are redundant and in part intertwined with their respective reciprocal projections. By deconstructing the interoceptive and exteroceptive components of affect- and stress related behavioral paradigms, evidence suggests that the PBN→CeA circuit modulates innate response to physical stimuli and fear conditioning. Conversely, the PBN→BNST circuit modulates distress-like stress in unpredictable contexts. Thereby, the PBN provides a pathway for alarming interoceptive and exteroceptive stimuli to be processed and relayed to the EA to induce stress-relevant affect. Additionally, we provide a framework for future studies to detail the cell-type specific intricacies of PBN→EA circuits in mediating behavioral responses to threats, and the relevance of the PBN in drug-use as it relates to threat and negative reinforcement. This article is part of the special Issue on 'Neurocircuitry Modulating Drug and Alcohol Abuse'. Highlights: Parabrachial to extended amygdala circuit (PBN.→EA) modulates stress-related consumption. PBN.→EA modulates innate and learned fear behavior. PBN.→EA activity is dysregulated in visceral and somatosensory disorders. PBN.→EA driven behavior and transmission is sensitive to chronic stress. Stress-like behavior driven by PBN.→EA is relevant to drug-related negative-affect.