Fear circuit-based neurobehavioral signatures mirror resilience to chronic social stress in mouse

Consistent evidence from human data points to successful threat-safety discrimination and responsiveness to extinction of fear memories as key characteristics of resilient individuals. To promote valid cross-species approaches for the identification of resilience mechanisms, we establish a translati...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2023-04, Vol.120 (17), p.e2205576120-e2205576120
Main Authors: Ayash, Sarah, Lingner, Thomas, Ramisch, Anna, Ryu, Soojin, Kalisch, Raffael, Schmitt, Ulrich, Müller, Marianne B
Format: Article
Language:English
Subjects:
Affect
Animals
Avoidance Learning
Biological Sciences
Circuits
Conditioning, Classical - physiology
Data points
Extinction behavior
Extinction, Psychological - physiology
Fear
Fear - physiology
Fear conditioning
Humans
Learning
Mice
Phenotypes
Resilience
Resistance to extinction
Safety
Social interactions
Stratification
Stress, Psychological - genetics
Subgroups
Transcriptomes
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Summary:Consistent evidence from human data points to successful threat-safety discrimination and responsiveness to extinction of fear memories as key characteristics of resilient individuals. To promote valid cross-species approaches for the identification of resilience mechanisms, we establish a translationally informed mouse model enabling the stratification of mice into three phenotypic subgroups following chronic social defeat stress, based on their individual ability for threat-safety discrimination and conditioned learning: the , characterized by successful social threat-safety discrimination and extinction of social aversive memories; the , showing aversive response generalization and resistance to extinction, in line with findings on susceptible individuals; and the displaying impaired aversive conditioned learning. To explore the neurobiological mechanisms underlying the stratification, we perform transcriptome analysis within three key target regions of the fear circuitry. We identify subgroup-specific differentially expressed genes and gene networks underlying the behavioral phenotypes, i.e., the individual ability to show threat-safety discrimination and respond to extinction training. Our approach provides a translationally informed template with which to characterize the behavioral, molecular, and circuit bases of resilience in mice.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2205576120