Serotonin deficiency increases context-dependent fear learning through modulation of hippocampal activity
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- 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.…
Autor(en): | 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 |
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URN: | urn:nbn:de:bvb:20-opus-196077 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Frontiers in Neuroscience |
ISSN: | 1662-453X |
Erscheinungsjahr: | 2019 |
Band / Jahrgang: | 13 |
Heft / Ausgabe: | 245 |
Originalveröffentlichung / Quelle: | Frontiers in Neuroscience, 2019, 13:245. doi: 10.3389/fnins.2019.00245 |
DOI: | https://doi.org/10.3389/fnins.2019.00245 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | extinction; fear learning; hippocampus; immediate-early gene; knockout; long-term potentiation; serotonin deficiency; tryptophan hydroxylase 2 |
Datum der Freischaltung: | 03.03.2020 |
Datum der Erstveröffentlichung: | 24.04.2019 |
EU-Projektnummer / Contract (GA) number: | 602805 |
EU-Projektnummer / Contract (GA) number: | 728018 |
OpenAIRE: | OpenAIRE |
Open-Access-Publikationsfonds / Förderzeitraum 2019 | |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |