AUTHOR=Waider Jonas , Popp Sandy , Mlinar Boris , Montalbano Alberto , Bonfiglio Francesco , Aboagye Benjamin , Thuy Elisabeth , Kern Raphael , Thiel Christopher , Araragi Naozumi , Svirin Evgeniy , Schmitt-Böhrer Angelika G. , Corradetti Renato , Lowry Christopher A. , Lesch Klaus-Peter 

TITLE=Serotonin Deficiency Increases Context-Dependent Fear Learning Through Modulation of Hippocampal Activity

JOURNAL=Frontiers in Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2019.00245

DOI=10.3389/fnins.2019.00245

ISSN=1662-453X

ABSTRACT=<p>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 (<italic>Tph2</italic>) 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). <italic>Tph2</italic> 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.</p>