title: Synaptic integration of transplanted interneuron progenitor cells into native cortical networks.
abstract: Interneuron-based cell transplantation is a powerful method to modify network function in a variety of neurological disorders, including epilepsy. Whether new interneurons integrate into native neural networks in a subtype-specific manner is not well understood, and the therapeutic mechanisms underlying interneuron-based cell therapy, including the role of synaptic inhibition, are debated. In this study, we tested subtype-specific integration of transplanted interneurons using acute cortical brain slices and visualized patch-clamp recordings to measure excitatory synaptic inputs, intrinsic properties, and inhibitory synaptic outputs. Fluorescently labeled progenitor cells from the embryonic medial ganglionic eminence (MGE) were used for transplantation. At 5 wk after transplantation, MGE-derived parvalbumin-positive (PV+) interneurons received excitatory synaptic inputs, exhibited mature interneuron firing properties, and made functional synaptic inhibitory connections to native pyramidal cells that were comparable to those of native PV+ interneurons. These findings demonstrate that MGE-derived PV+ interneurons functionally integrate into subtype-appropriate physiological niches within host networks following transplantation.
authors.affiliation: Epilepsy Research Laboratory in the Department of Neurological Surgery, University of California, San Francisco, California.
authors.forename: MacKenzie A
authors.initials: MA
authors.lastname: Howard
authors.affiliation: Epilepsy Research Laboratory in the Department of Neurological Surgery, University of California, San Francisco, California scott.baraban@ucsf.edu.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Baraban
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000601:surgery*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D007395:Interneurons / Q000637:transplantation*; D008473:Median Eminence / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D033581:Stem Cell Transplantation
chemical_list: D010320:Parvalbumins; D049452:Green Fluorescent Proteins
keywords: cell therapy; interneuron; medial ganglionic eminence; neural transplant; synaptic integration