Electrophysiological investigations of synaptic connectivity between host and graft neurons

The functional synaptic integration of grafted stem cell-derived neurons is one of the key aspects of neural cell replacement therapies for neurological disorders such as Parkinson's disease. However, little is currently known about the synaptic connectivity between graft and host cells after transplantation, not only in the settings of clinical trials but also in experimental studies. This knowledge gap is primarily due to the lack of experimental electrophysiological approaches allowing interrogation of synaptic connectivity between prospectively identified host and graft neurons and hampers our understanding of the mechanisms underlying functional integration of stem cell-derived neurons in the host brain, as well as the optimization of protocols for deriving stem cells for neural cell replacement therapy. Recent optogenetic tools allow for direct investigation of connectivity between host and graft neural populations and have already been applied to show bidirectional integration of dopaminergic neurons in a host tissue. These new tools have potential to advance our understanding of functional integration in the near future. Here, we provide an overview of the current literature addressing functional integration of stem cell-derived neurons in the settings of Parkinson's disease models and discuss some experimental paradigms to approach this issue.