The DOI matches its Crossref record; 102 of the 104 references it cites were found in a registry or an index.
Social Defeat: Impact on Fear Extinction and Amygdala-Prefrontal Cortical Theta Synchrony in 5-HTT Deficient Mice
Open accessAbstract
Emotions, such as fear and anxiety, can be modulated by both environmental and genetic factors. One genetic factor is for example the genetically encoded variation of the serotonin transporter (5-HTT) expression. In this context, the 5-HTT plays a key role in the regulation of central 5-HT neurotransmission, which is critically involved in the physiological regulation of emotions including fear and anxiety. However, a systematic study which examines the combined influence of environmental and genetic factors on fear-related behavior and the underlying neurophysiological basis is missing. Therefore, in this study we used the 5-HTT-deficient mouse model for studying emotional dysregulation to evaluate consequences of genotype specific disruption of 5-HTT function and repeated social defeat for fear-related behaviors and corresponding neurophysiological activities in the lateral amygdala (LA) and infralimbic region of the medial prefrontal cortex (mPFC) in male 5-HTT wild-type (+/+), homo- (-/-) and heterozygous (+/-) mice. Naive males and experienced losers (generated in a resident-intruder paradigm) of all three genotypes, unilaterally equipped with recording electrodes in LA and mPFC, underwent a Pavlovian fear conditioning. Fear memory and extinction of conditioned fear was examined while recording neuronal activity simultaneously with fear-related behavior. Compared to naive 5-HTT+/+ and +/- mice, 5-HTT-/- mice showed impaired recall of extinction. In addition, 5-HTT-/- and +/- experienced losers showed delayed extinction learning and impaired recall of extinction. Impaired behavioral responses were accompanied by increased theta synchronization between the LA and mPFC during extinction learning in 5-HTT-/- and +/- losers. Furthermore, impaired extinction recall was accompanied with increased theta synchronization in 5-HTT-/- naive and in 5-HTT-/- and +/- loser mice. In conclusion, extinction learning and memory of conditioned fear can be modulated by both the 5-HTT gene activity and social experiences in adulthood, accompanied by corresponding alterations of the theta activity in the amygdala-prefrontal cortex network.
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“Brain reward pathways, including the ventral tegmental area (VTA) and the nucleus accumbens (NAc) (4) as well as the prefrontal cortex (PFC) and the amygdala (11,12), have been implicated in the neural circuitry mediating these differences in stress susceptibility.”
From Neuroanatomic differences associated with stress susceptibility and resilience (2016) · cites this paper as [11]
In the citing paper
“Social defeat–induced anxiety and depressive-like behaviors were previously associated with decreased neuronal activity in the medial PFC (46) as well as increased VTA and amygdala activity (10–12).”
From Neuroanatomic differences associated with stress susceptibility and resilience (2016) · cites this paper as [11]
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Animal models of post-traumatic stress disorder:
Heltzel, L. C. M. W., & Homberg, J. R. (2019) · Oxford University Press eBooks · doi:10.1093/oso/9780198793014.003.0022
Mecca, F. F. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2019.tde-27052020-074722
Moghimzadeh-Mohebbi, P., Sohrabi, M. M., & Mazloom, R. (2024) · Medical Hypotheses · doi:10.1016/j.mehy.2024.111486
Metadata
- Authors
- Narayanan, V., Heiming, R. S., Jansen, F., Lesting, J., Sachser, N., Pape, H.-C., & Seidenbecher, T.
- Affiliations
- University of Münster (DE)
- Corresponding author
- Seidenbecher, Thomas
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-07-27
- Volume
- 6
- Issue
- 7
- Pages
- e22600
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3144906
- OpenAlex
- W2051845141
- Cited by
- 103
- References
- 104
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 6 · 2016: 6 · 2015: 8 · 2014: 9 · 2013: 22 · 2012: 8
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (TRR‐58, TP A01, SFB TRR 58)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- social defeat, fear extinction, serotonin transporter, 5-HTT knockout mice, lateral amygdala, medial prefrontal cortex, infralimbic cortex, theta synchronization, fear conditioning, fear memory, resident-intruder paradigm, emotional dysregulation, extinction recall
- MeSH terms
- Action Potentials, Amygdala, Animals, Cortical Synchronization, Extinction, Psychological, Fear, Genotype, Male, Nerve Net, Mental Recall, Social Behavior, Prefrontal Cortex, Mice, Knockout, Freezing Reaction, Cataleptic, Serotonin Plasma Membrane Transport Proteins, Mice
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