Know safety, no fear

Abstract

Every day we are bombarded by stimuli that must be assessed for their potential for harm or benefit. Once a stimulus is learned to predict harm, it can elicit fear responses. Such learning can last a lifetime but is not always beneficial for an organism. For an organism to thrive in its environment, it must know when to engage in defensive, avoidance behaviors and when to engage in non-defensive, approach behaviors. Fear should be suppressed in situations that are not dangerous: when a novel, innocuous stimulus resembles a feared stimulus, when a feared stimulus no longer predicts harm, or when there is an option to avoid harm. A cardinal feature of anxiety disorders is the inability to suppress fear adaptively. In PTSD, for instance, learned fear is expressed inappropriately in safe situations and is resistant to extinction. In this review, we discuss mechanisms of suppressing fear responses during stimulus discrimination, fear extinction, and active avoidance, focusing on the well-studied tripartite circuit consisting of the amygdala, medial prefrontal cortex and hippocampus.

The Role of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Signaling in the Hippocampal Dentate Gyrus

“…However, dysregulated fear extinction and fear discrimination are also hallmark features of PTSD (see Jovanovic et al, 2012;Sangha et al, 2020), and rs2267735 was also associated with compromised extinction and reduced discrimination between fear-conditioned stimuli (Ressler et al, 2011;Pohlack et al, 2015;Mercer et al, 2016;Ramikie and Ressler, 2016). These data suggest that PACAP dysregulation has effects in multiple neural circuits associated with PTSD symptoms, which may include regions of the amygdala, medial prefrontal cortex (mPFC) and hippocampus.…”

Public Health Lessons Learned From Biases in Coronavirus Mortality Overestimation

“…63 Even if a threat ceases to exist, prolonged fearful avoidance of threats is maladaptive and restricts a return to normal social interaction and productivity. 64 For example, after the outbreak of SARS had ended in 2004, avoidance behavior continued to restrict people's social interactions and prevented people from returning to work. 65 Exaggerated levels of fear were driven by sensationalist media coverage during the COVID-19 pandemic.…”

Assaying Fear Memory Discrimination and Generalization: Methods and Concepts

“…Variations of the differential fear conditioning paradigm have been used to study "safety" learning and memory (Foilb, Flyer-Adams, Maier, & Christianson, 2016;Greiner, Müller, Norris, Ng, & Sangha, 2019;Müller, Brinkman, Sowinski, & Sangha, 2018;Sangha, Chadick, & Janak, 2013). While the various procedures for safety learning are outside of the scope of this methods article, there are several reviews on the topic (Christianson et al, 2012;Sangha et al, 2020). Outlined here are two methods for studying safety learning.…”

“…Numerous brain systems have been demonstrated to contribute to fear discrimination and generalization processing, including the cingulate cortex (Ortiz et al., ), hippocampus (Besnard & Sahay, ), amygdala (Ciocchi et al., ; Ghosh & Chattarji, ; Grosso, Santoni, Manassero, Renna, & Sacchetti, ), thalamic and subthalamic nuclei (Ferrara, Cullen, Pullins, Rotondo, & Helmstetter, ; Ramanathan, Ressler, Jin, & Maren, ; Venkataraman et al., ; Xu & Sudhof, ), midbrain (Rozeske et al., ), and prefrontal cortices (Fitzgerald et al., ; Pollack et al., ; Rozeske et al., ; Scarlata et al., ). For a review on the neurobiology of fear generalization, see Asok, Kandel, and Rayman () and Sangha, Diehl, Bergstrom, and Drew ().…”