TY  - JOUR
A1  - Waider, Jonas
A1  - Popp, Sandy
A1  - Mlinar, Boris
A1  - Montalbano, Alberto
A1  - Bonfiglio, Francesco
A1  - Aboagye, Benjamin
A1  - Thuy, Elisabeth
A1  - Kern, Raphael
A1  - Thiel, Christopher
A1  - Araragi, Naozumi
A1  - Svirin, Evgeniy
A1  - Schmitt-Böhrer, Angelika G.
A1  - Corradetti, Renato
A1  - Lowry, Christopher A.
A1  - Lesch, Klaus-Peter
T1  - Serotonin deficiency increases context-dependent fear learning through modulation of hippocampal activity
JF  - Frontiers in Neuroscience
N2  - 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.
KW  - tryptophan hydroxylase 2
KW  - knockout
KW  - fear learning
KW  - extinction
KW  - long-term potentiation
KW  - hippocampus
KW  - immediate-early gene
KW  - serotonin deficiency
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196077
SN  - 1662-453X
VL  - 13
IS  - 245
ER  -