title: Connectivity and circuitry in a dish versus in a brain.
abstract: In order to understand and find therapeutic strategies for neurological disorders, disease models that recapitulate the connectivity and circuitry of patients' brain are needed. Owing to many limitations of animal disease models, in vitro neuronal models using patient-derived stem cells are currently being developed. However, prior to employing neurons as a model in a dish, they need to be evaluated for their electrophysiological properties, including both passive and active membrane properties, dynamics of neurotransmitter release, and capacity to undergo synaptic plasticity. In this review, we survey recent attempts to study these issues in human induced pluripotent stem cell-derived neurons. Although progress has been made, there are still many hurdles to overcome before human induced pluripotent stem cell-derived neurons can fully recapitulate all of the above physiological properties of adult mature neurons. Moreover, proper integration of neurons into pre-existing circuitry still needs to be achieved. Nevertheless, in vitro neuronal stem cell-derived models hold great promise for clinical application in neurological diseases in the future.
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032 USA ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain P&S Bldg, Room 12-420D, Columbia University, New York, NY 10032 USA ; Columbia Stem Cell Initiative, CUMC, New York, NY 10032 USA ; Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom 73170 Thailand.
authors.forename: Vorapin
authors.initials: V
authors.lastname: Chinchalongporn
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032 USA ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain P&S Bldg, Room 12-420D, Columbia University, New York, NY 10032 USA ; Columbia Stem Cell Initiative, CUMC, New York, NY 10032 USA ; Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Koppensteiner
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032 USA ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain P&S Bldg, Room 12-420D, Columbia University, New York, NY 10032 USA ; Columbia Stem Cell Initiative, CUMC, New York, NY 10032 USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Prè
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom 73170 Thailand.
authors.forename: Wipawan
authors.initials: W
authors.lastname: Thangnipon
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032 USA ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain P&S Bldg, Room 12-420D, Columbia University, New York, NY 10032 USA ; Columbia Stem Cell Initiative, CUMC, New York, NY 10032 USA ; Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University of Naples, 80131 Naples, Italy.
authors.forename: Leonilda
authors.initials: L
authors.lastname: Bilo
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032 USA ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain P&S Bldg, Room 12-420D, Columbia University, New York, NY 10032 USA ; Columbia Stem Cell Initiative, CUMC, New York, NY 10032 USA.
authors.forename: Ottavio
authors.initials: O
authors.lastname: Arancio