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

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-Boehrer, Renato Corradetti, Christopher A. Lowry, Klaus-Peter Lesch

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Web of Science)

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.

Original languageEnglish
Article number245
Number of pages12
JournalFrontiers in Neuroscience
Volume13
DOIs
Publication statusPublished - 24 Apr 2019

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

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