Synaptic plasticity in human thalamocortical assembloids
Mary H. Patton,
Kristen T. Thomas,
Ildar T. Bayazitov,
Kyle D. Newman,
Nathaniel B. Kurtz,
Camenzind G. Robinson,
Cody A. Ramirez,
Alexandra J. Trevisan,
Jay B. Bikoff,
Samuel T. Peters,
Shondra M. Pruett-Miller,
Yanbo Jiang,
Andrew B. Schild,
Anjana Nityanandam,
Stanislav S. Zakharenko
Affiliations
Mary H. Patton
Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Kristen T. Thomas
Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Ildar T. Bayazitov
Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Kyle D. Newman
Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Nathaniel B. Kurtz
Cell and Tissue Imaging Center, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Camenzind G. Robinson
Cell and Tissue Imaging Center, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Cody A. Ramirez
Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Alexandra J. Trevisan
Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Jay B. Bikoff
Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Samuel T. Peters
Center for Advanced Genome Engineering, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Shondra M. Pruett-Miller
Center for Advanced Genome Engineering, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Yanbo Jiang
Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Andrew B. Schild
Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Anjana Nityanandam
Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Stanislav S. Zakharenko
Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; Corresponding author
Summary: Synaptic plasticities, such as long-term potentiation (LTP) and depression (LTD), tune synaptic efficacy and are essential for learning and memory. Current studies of synaptic plasticity in humans are limited by a lack of adequate human models. Here, we modeled the thalamocortical system by fusing human induced pluripotent stem cell-derived thalamic and cortical organoids. Single-nucleus RNA sequencing revealed that >80% of cells in thalamic organoids were glutamatergic neurons. When fused to form thalamocortical assembloids, thalamic and cortical organoids formed reciprocal long-range axonal projections and reciprocal synapses detectable by light and electron microscopy, respectively. Using whole-cell patch-clamp electrophysiology and two-photon imaging, we characterized glutamatergic synaptic transmission. Thalamocortical and corticothalamic synapses displayed short-term plasticity analogous to that in animal models. LTP and LTD were reliably induced at both synapses; however, their mechanisms differed from those previously described in rodents. Thus, thalamocortical assembloids provide a model system for exploring synaptic plasticity in human circuits.
