Abstract
Learning to fear danger is essential for survival. However, overactive, relapsing fear behavior in the absence of danger is a hallmark of disabling anxiety disorders that affect millions of people. Its suppression is thus of great interest, but the necessary brain components remain incompletely identified. We studied fear suppression through a procedure in which, after acquiring fear of aversive events (fear learning), subjects were exposed to fear-eliciting cues without aversive events (safety learning), leading to suppression of fear behavior (fear extinction). Here we show that inappropriate, learning-resistant fear behavior results from disruption of brain components not previously implicated in this disorder: hypothalamic melanin-concentrating hormone-expressing neurons (MNs). Using real-time recordings of MNs across fear learning and extinction, we provide evidence that fear-inducing aversive events elevate MN activity. We find that optogenetic disruption of this MN activity profoundly impairs safety learning, abnormally slowing down fear extinction and exacerbating fear relapse. Importantly, we demonstrate that the MN disruption impairs neither fear learning nor related sensory responses, indicating that MNs differentially control safety and fear learning. Thus, we identify a neural substrate for inhibition of excessive fear behavior.
Highlights
IntroductionOveractive, relapsing fear behavior in the absence of danger is a hallmark of disabling anxiety disorders that affect millions of people
Learning to fear danger is essential for survival
Learningresistant fear results from disruption of brain components not previously implicated in this disorder: hypothalamic melaninconcentrating hormone–expressing neurons (MNs)
Summary
Overactive, relapsing fear behavior in the absence of danger is a hallmark of disabling anxiety disorders that affect millions of people. Pavlovian fear conditioning is one of the leading translational models for studying fear acquisition and subsequent suppression by extinction-based exposure therapy [12] In this procedure, after acquiring fear of aversive events (fear learning), subjects are exposed to fear-eliciting cues without aversive events (safety learning), leading to suppression of fear behavior (fear extinction) [1, 12]. Recent experimental evidence has led to the suggestion that MN activity may promote multiple forms of synaptic and behavioral flexibility through either learning or forgetting [20, 22,23,24,25] It is unknown if and when the endogenous MN activity regulates fear learning and/or extinction. The present study aimed to define endogenous MN activation patterns across the multiple phases of fear learning and extinction, and to test whether MN activity is causally linked to specific features of overactive fear behavior
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.