ArticleMolecular psychiatry2019
Identification of a novel gene regulating amygdala-mediated fear extinction.
Article in Molecular psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 39 citations in OpenAlex.
- Phospholipase A2 downregulates inhibitory transmission in the amygdala and impairs fear extinction.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Sex chromosome genes contribute to cocaine vulnerability in a strain-dependent manner.Research square · 2026Article
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- Enhanced fear extinction through infralimbic perineuronal net digestion: The modulatory role of adolescent alcohol exposure.Alcohol (Fayetteville, N.Y.) · 2025Article
- Characteristics of gut microbiota dysbiosis in patients with colorectal polyps.World journal of gastrointestinal oncology · 2025Article
- Enhanced Fear Extinction Through Infralimbic Perineuronal Net Digestion: The Modulatory Role of Adolescent Alcohol Exposure.bioRxiv : the preprint server for biology · 2024Article
- Leveraging interindividual variability in threat conditioning of inbred mice to model trait anxiety.PLoS biology · 2024Article
- Fear conditioning and extinction distinctively alter bidirectional synaptic plasticity within the amygdala of an animal model of post-traumatic stress disorder.Neurobiology of stress · 2024Article
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- Investigating Neural Correlates of Behavior Through In Vivo Electrophysiology.Current protocols · 2023Article
- Hunting for Genes Underlying Emotionality in the Laboratory Rat: Maps, Tools and Traps.Current neuropharmacology · 2023Review
- The extracellular matrix and perineuronal nets in memory.Molecular psychiatry · 2022Review
- Contributions of glucocorticoid receptors in cortical astrocytes to memory recall.Learning & memory (Cold Spring Harbor, N.Y.) · 2021Article
- Effects of optogenetic photoexcitation of infralimbic cortex inputs to the basolateral amygdala on conditioned fear and extinction.Behavioural brain research · 2021Article
- Turning strains into strengths for understanding psychiatric disorders.Molecular psychiatry · 2020Review
- Deficits across multiple behavioral domains align with susceptibility to stress in 129S1/SvImJ mice.Neurobiology of stress · 2020Article
- Improved visual discrimination learning in mice with partial 5-HT2B gene deletion.Neuroscience letters · 2020Article
- Dorsolateral striatum engagement during reversal learning.Learning & memory (Cold Spring Harbor, N.Y.) · 2020Article
- Selective sub-nucleus effects of intra-amygdala oxytocin on fear extinction.Behavioural brain research · 2020Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Recent years have seen advances in our understanding of the neural circuits associated with trauma-related disorders, and the development of relevant assays for these behaviors in rodents. Although inherited factors are known to influence individual differences in risk for these disorders, it has been difficult to identify specific genes that moderate circuit functions to affect trauma-related behaviors. Here, we exploited robust inbred mouse strain differences in Pavlovian fear extinction to uncover quantitative trait loci (QTL) associated with this trait. We found these strain differences to be resistant to developmental cross-fostering and associated with anatomical variation in basolateral amygdala (BLA) perineuronal nets, which are developmentally implicated in extinction. Next, by profiling extinction-driven BLA expression of QTL-linked genes, we nominated Ppid (peptidylprolyl isomerase D, a member of the tetratricopeptide repeat (TPR) protein family) as an extinction-related candidate gene. We then showed that Ppid was enriched in excitatory and inhibitory BLA neuronal populations, but at lower levels in the extinction-impaired mouse strain. Using a virus-based approach to directly regulate Ppid function, we demonstrated that downregulating BLA-Ppid impaired extinction, while upregulating BLA-Ppid facilitated extinction and altered in vivo neuronal extinction encoding. Next, we showed that Ppid colocalized with the glucocorticoid receptor (GR) in BLA neurons and found that the extinction-facilitating effects of Ppid upregulation were blocked by a GR antagonist. Collectively, our results identify Ppid as a novel gene involved in regulating extinction via functional actions in the BLA, with possible implications for understanding genetic and pathophysiological mechanisms underlying risk for trauma-related disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.