@article{095560c96a7c42908b89035c2d61a0aa,
title = "Serotonin Deficiency Increases Context-Dependent Fear Learning Through Modulation of Hippocampal Activity",
abstract = "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 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.",
keywords = "5-HT, AMYGDALA, ANXIETY DISORDERS, DORSAL, ENDOGENOUS SEROTONIN, FREEZING BEHAVIOR, GENERALIZED ANXIETY, LONG-TERM POTENTIATION, NEURONS, STRESS, extinction, fear learning, hippocampus, immediate-early gene, knockout, long-term potentiation, serotonin deficiency, tryptophan hydroxylase 2, DISORDERS",
author = "Jonas Waider and Sandy Popp and Boris Mlinar and Alberto Montalbano and Francesco Bonfiglio and Benjamin Aboagye and Elisabeth Thuy and Raphael Kern and Christopher Thiel and Naozumi Araragi and Evgeniy Svirin and Schmitt-Boehrer, {Angelika G.} and Renato Corradetti and Lowry, {Christopher A.} and Klaus-Peter Lesch",
note = "Funding Information: This study was supported by the German Research Foundation (DFG: SFB TRR58-A05 to KPL and WA 3446/2-1 to JW), the European Union's Seventh Framework Program (FP7/2007-2013) under Grant No. 602805 (Aggressotype), the Horizon 2020 Research and Innovation Program under Grant No. 728018 (Eat2beNICE), the 5-100 Russian Academic Excellence Project (to KPL) and the University of Florence (ex60% to RC). Funding Information: This study was supported by the German Research Foundation (DFG: SFB TRR58-A05 to KPL and WA 3446/2-1 to JW), the European Union{\textquoteright}s Seventh Framework Program (FP7/2007– 2013) under Grant No. 602805 (Aggressotype), the Horizon 2020 Research and Innovation Program under Grant No. 728018 (Eat2beNICE), the 5-100 Russian Academic Excellence Project (to KPL) and the University of Florence (ex60% to RC). Publisher Copyright: {\textcopyright} 2019 Waider, Popp, Mlinar, Montalbano, Bonfiglio, Aboagye, Thuy, Kern, Thiel, Araragi, Svirin, Schmitt-B{\"o}hrer, Corradetti, Lowry and Lesch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.",
year = "2019",
month = apr,
day = "24",
doi = "10.3389/fnins.2019.00245",
language = "English",
volume = "13",
journal = "Frontiers in Neuroscience",
issn = "1662-453X",
publisher = "Frontiers Media S.A.",
}