Neuronal activity triggers uptake of hematopoietic extracellular vesicles in vivo

PLoS Biol. 2020 Mar 16;18(3):e3000643. doi: 10.1371/journal.pbio.3000643. eCollection 2020 Mar.


Communication with the hematopoietic system is a vital component of regulating brain function in health and disease. Traditionally, the major routes considered for this neuroimmune communication are by individual molecules such as cytokines carried by blood, by neural transmission, or, in more severe pathologies, by the entry of peripheral immune cells into the brain. In addition, functional mRNA from peripheral blood can be directly transferred to neurons via extracellular vesicles (EVs), but the parameters that determine their uptake are unknown. Using varied animal models that stimulate neuronal activity by peripheral inflammation, optogenetics, and selective proteasome inhibition of dopaminergic (DA) neurons, we show that the transfer of EVs from blood is triggered by neuronal activity in vivo. Importantly, this transfer occurs not only in pathological stimulation but also by neuronal activation caused by the physiological stimulus of novel object placement. This discovery suggests a continuous role of EVs under pathological conditions as well as during routine cognitive tasks in the healthy brain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Cells / cytology*
  • Blood Cells / metabolism
  • Brain / drug effects
  • Brain / metabolism*
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Extracellular Vesicles / metabolism*
  • Female
  • Hippocampus / physiology
  • Inflammation / chemically induced
  • Inflammation / metabolism*
  • Kainic Acid / pharmacology
  • Lipopolysaccharides / toxicity
  • Male
  • Mice, Transgenic
  • Optogenetics
  • Proteasome Endopeptidase Complex / metabolism
  • Signal Transduction
  • Stereotaxic Techniques
  • Ubiquitin / metabolism


  • Lipopolysaccharides
  • Ubiquitin
  • Proteasome Endopeptidase Complex
  • Kainic Acid