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Serotonin deficiency increases context-dependent fear learning through modulation of hippocampal activity

Please always quote using this URN: urn:nbn:de:bvb:20-opus-196077
  • Brain serotonin (5-hydroxytryptamine, 5-HT) system dysfunction is implicated in exaggerated fear responses triggering various anxiety-, stress-, and trauma-related disorders. However, the underlying mechanisms are not well understood. Here, we investigated the impact of constitutively inactivated 5-HT synthesis on context-dependent fear learning and extinction using tryptophan hydroxylase 2 (Tph2) knockout mice. Fear conditioning and context-dependent fear memory extinction paradigms were combined with c-Fos imaging and electrophysiologicalBrain serotonin (5-hydroxytryptamine, 5-HT) system dysfunction is implicated in exaggerated fear responses triggering various anxiety-, stress-, and trauma-related disorders. However, the underlying mechanisms are not well understood. Here, we investigated the impact of constitutively inactivated 5-HT synthesis on context-dependent fear learning and extinction using tryptophan hydroxylase 2 (Tph2) knockout mice. Fear conditioning and context-dependent fear memory extinction paradigms were combined with c-Fos imaging and electrophysiological recordings in the dorsal hippocampus (dHip). Tph2 mutant mice, completely devoid of 5-HT synthesis in brain, displayed accelerated fear memory formation and increased locomotor responses to foot shock. Furthermore, recall of context-dependent fear memory was increased. The behavioral responses were associated with increased c-Fos expression in the dHip and resistance to foot shock-induced impairment of hippocampal long-term potentiation (LTP). In conclusion, increased context-dependent fear memory resulting from brain 5-HT deficiency involves dysfunction of the hippocampal circuitry controlling contextual representation of fear-related behavioral responses.show moreshow less

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Metadaten
Author: Jonas Waider, Sandy Popp, Boris Mlinar, Alberto Montalbano, Francesco Bonfiglio, Benjamin Aboagye, Elisabeth Thuy, Raphael Kern, Christopher Thiel, Naozumi Araragi, Evgeniy Svirin, Angelika G. Schmitt-Böhrer, Renato Corradetti, Christopher A. Lowry, Klaus-Peter Lesch
URN:urn:nbn:de:bvb:20-opus-196077
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Language:English
Parent Title (English):Frontiers in Neuroscience
ISSN:1662-453X
Year of Completion:2019
Volume:13
Issue:245
Source:Frontiers in Neuroscience, 2019, 13:245. doi: 10.3389/fnins.2019.00245
DOI:https://doi.org/10.3389/fnins.2019.00245
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:extinction; fear learning; hippocampus; immediate-early gene; knockout; long-term potentiation; serotonin deficiency; tryptophan hydroxylase 2
Release Date:2020/03/03
Date of first Publication:2019/04/24
EU-Project number / Contract (GA) number:602805
EU-Project number / Contract (GA) number:728018
OpenAIRE:OpenAIRE
Open-Access-Publikationsfonds / Förderzeitraum 2019
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International