Metabolic tuning of inhibition regulates hippocampal neurogenesis in the adult brain

Xinxing Wang, Hanxiao Liu, Johannes Morstein, Alexander J.E. Novak, Dirk Trauner, Qiaojie Xiong, Yuguo Yu, Shaoyu Ge

Research output: Contribution to journalArticlepeer-review


Hippocampus-engaged behaviors stimulate neurogenesis in the adult dentate gyrus by largely unknown means. To explore the underlying mechanisms, we used tetrode recording to analyze neuronal activity in the dentate gyrus of freely moving adult mice during hippocampus-engaged contextual exploration. We found that exploration induced an overall sustained increase in inhibitory neuron activity that was concomitant with decreased excitatory neuron activity. A mathematical model based on energy homeostasis in the dentate gyrus showed that enhanced inhibition and decreased excitation resulted in a similar increase in neurogenesis to that observed experimentally. To mechanistically investigate this sustained inhibitory regulation, we performed metabolomic and lipidomic profiling of the hippocampus during exploration. We found sustainably increased signaling of sphingosine-1-phosphate, a bioactive metabolite, during exploration. Furthermore, we found that sphingosine-1-phosphate signaling through its receptor 2 increased interneuron activity and thus mediated exploration-induced neurogenesis. Taken together, our findings point to a behavior-metabolism circuit pathway through which experience regulates adult hippocampal neurogenesis.

Original languageEnglish (US)
Pages (from-to)25818-25829
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
StatePublished - Oct 13 2020


  • Adult hippocampal neurogenesis
  • Metabolic regulation
  • Neurocircuit
  • Tetrode recording

ASJC Scopus subject areas

  • General


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