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

Autor: Waider J; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany., Popp S; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany., Mlinar B; Department of Neuroscience, Psychology, Drug Research, and Child Health, University of Florence, Florence, Italy., Montalbano A; Department of Neuroscience, Psychology, Drug Research, and Child Health, University of Florence, Florence, Italy., Bonfiglio F; Department of Neuroscience, Psychology, Drug Research, and Child Health, University of Florence, Florence, Italy., Aboagye B; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany., Thuy E; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany., Kern R; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany., Thiel C; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany., Araragi N; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; Charité - Universitätsmedizin Berlin, Berlin, Germany., Svirin E; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia., Schmitt-Böhrer AG; Department of Psychiatry, Psychosomatics, and Psychotherapy, Center of Mental Health, University of Würzburg, Würzburg, Germany., Corradetti R; Department of Neuroscience, Psychology, Drug Research, and Child Health, University of Florence, Florence, Italy., Lowry CA; Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, United States., Lesch KP; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.; Department of Translational Psychiatry, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
Jazyk: angličtina
Zdroj: Frontiers in neuroscience [Front Neurosci] 2019 Apr 24; Vol. 13, pp. 245. Date of Electronic Publication: 2019 Apr 24 (Print Publication: 2019).
DOI: 10.3389/fnins.2019.00245
Abstrakt: 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.
Databáze: MEDLINE