Serotonin of mast cell origin contributes to hippocampal function

Katherine M. Nautiyal, Christopher A. Dailey, Jaquelyn L. Jahn, Elizabeth Rodriquez, Nguyen Hong Son, Jonathan V. Sweedler, Rae Silver

Research output: Contribution to journalArticlepeer-review


In the central nervous system, serotonin, an important neurotransmitter and trophic factor, is synthesized by both mast cells and neurons. Mast cells, like other immune cells, are born in the bone marrow and migrate to many tissues. We show that they are resident in the mouse brain throughout development and adulthood. Measurements based on capillary electrophoresis with native fluorescence detection indicate that a significant contribution of serotonin to the hippocampal milieu is associated with mast cell activation. Compared with their littermates, mast cell-deficient C57BL/6 KitW-sh/W-sh mice have profound deficits in hippocampus-dependent spatial learning and memory and in hippocampal neurogenesis. These deficits are associated with a reduction in cell proliferation and in immature neurons in the dentate gyrus, but not in the subventricular zone - a neurogenic niche lacking mast cells. Chronic treatment with fluoxetine, a selective serotonin reuptake inhibitor, reverses the deficit in hippocampal neurogenesis in mast cell-deficient mice. In summary, the present study demonstrates that mast cells are a source of serotonin, that mast cell-deficient C57BL/6 KitW-sh/W-sh mice have disrupted hippocampus-dependent behavior and neurogenesis, and that elevating serotonin in these mice, by treatment with fluoxetine, reverses these deficits. We conclude that mast cells contribute to behavioral and physiological functions of the hippocampus and note that they play a physiological role in neuroimmune interactions, even in the absence of inflammatory responses. Mast cells are immune cells that are resident in the mouse brain within and near the hippocampus throughout development and adulthood. Their activation contributes serotonin to the hippocampus. A lack of mast cells is associated with deficits in spatial learning and memory and decreased hippocampal neurogenesis which can be restored through administration of the selective serotonin reuptake inhibitor fluoxetine.

Original languageEnglish (US)
Pages (from-to)2347-2359
Number of pages13
JournalEuropean Journal of Neuroscience
Issue number3
StatePublished - Aug 2012


  • Hippocampus
  • Neurogenesis
  • Psychoneuroimmunology
  • Serotonin
  • Spatial learning

ASJC Scopus subject areas

  • General Neuroscience


Dive into the research topics of 'Serotonin of mast cell origin contributes to hippocampal function'. Together they form a unique fingerprint.

Cite this