Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca2+-permeable TRPC6 channels

Kristina Leuner*, Wei Li, Michelle D. Amaral, Stephanie Rudolph, Gaston Calfa, Anita M. Schuwald, Christian Harteneck, Takafumi Inoue, Lucas Pozzo-Miller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


The standardized extract of the St. John's wort plant (Hypericum perforatum) is commonly used to treat mild to moderate depression. Its active constituent is hyperforin, a phloroglucinol derivative that reduces the reuptake of serotonin and norepinephrine by increasing intracellular Na+ concentration through the activation of nonselective cationic TRPC6 channels. TRPC6 channels are also Ca2+-permeable, resulting in intracellular Ca2+ elevations. Indeed, hyperforin activates TRPC6-mediated currents and Ca2+ transients in rat PC12 cells, which induce their differentiation, mimicking the neurotrophic effect of nerve growth factor. Here, we show that hyperforin modulates dendritic spine morphology in CA1 and CA3 pyramidal neurons of hippocampal slice cultures through the activation of TRPC6 channels. Hyperforin also evoked intracellular Ca2+ transients and depolarizing inward currents sensitive to the TRPC channel blocker La3+, thus resembling the actions of the neurotrophin brain-derived neurotrophic factor (BDNF) in hippocampal pyramidal neurons. These results suggest that the antidepressant actions of St. John's wort are mediated by a mechanism similar to that engaged by BDNF.

Original languageEnglish
Pages (from-to)40-52
Number of pages13
Issue number1
Publication statusPublished - 2013 Jan


  • Biolistic transfection
  • CA1 pyramidal neuron
  • CA3 pyramidal neuron
  • Confocal microscopy
  • Hippocampus
  • Organotypic slice culture
  • SiRNA-mediated knockdown
  • TRPC6

ASJC Scopus subject areas

  • Cognitive Neuroscience


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