Frontiers in Neuroscience (Apr 2019)

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,
  • Naozumi Araragi,
  • Evgeniy Svirin,
  • Evgeniy Svirin,
  • Angelika G. Schmitt-Böhrer,
  • Renato Corradetti,
  • Christopher A. Lowry,
  • Klaus-Peter Lesch,
  • Klaus-Peter Lesch,
  • Klaus-Peter Lesch

DOI
https://doi.org/10.3389/fnins.2019.00245
Journal volume & issue
Vol. 13

Abstract

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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.

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