Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons

Research output: Contribution to journalJournal articleResearchpeer-review

  • Shane Grealish
  • Andreas Heuer
  • Tiago Cardoso
  • Kirkeby, Agnete
  • Marie Jönsson
  • Jenny Johansson
  • Anders Björklund
  • Johan Jakobsson
  • Malin Parmar

Human embryonic stem cell (hESC)-derived dopamine neurons are currently moving toward clinical use for Parkinson's disease (PD). However, the timing and extent at which stem cell-derived neurons functionally integrate into existing host neural circuitry after transplantation remain largely unknown. In this study, we use modified rabies virus to trace afferent and efferent connectivity of transplanted hESC-derived neurons in a rat model of PD and report that grafted human neurons integrate into the host neural circuitry in an unexpectedly rapid and extensive manner. The pattern of connectivity resembled that of local endogenous neurons, while ectopic connections were not detected. Revealing circuit integration of human dopamine neurons substantiates their potential use in clinical trials. Additionally, our data present rabies-based tracing as a valuable and widely applicable tool for analyzing graft connectivity that can easily be adapted to analyze connectivity of a variety of different neuronal sources and subtypes in different disease models.

Original languageEnglish
JournalStem Cell Reports
Volume4
Issue number6
Pages (from-to)975-983
Number of pages9
ISSN2213-6711
DOIs
Publication statusPublished - 9 Jun 2015

ID: 228506094