Synaptic plasticity in human thalamocortical assembloids.

Autor:	Patton MH; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Thomas KT; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Bayazitov IT; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Newman KD; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Kurtz NB; Cell and Tissue Imaging Center, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Robinson CG; Cell and Tissue Imaging Center, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Ramirez CA; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Trevisan AJ; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Bikoff JB; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Peters ST; Center for Advanced Genome Engineering, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Pruett-Miller SM; 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., Jiang Y; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Schild AB; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Nityanandam A; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Zakharenko SS; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: stanislav.zakharenko@stjude.org.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Aug 27; Vol. 43 (8), pp. 114503. Date of Electronic Publication: 2024 Jul 16.
DOI:	10.1016/j.celrep.2024.114503
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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