Biology subjects

Takeuchi, R. F.

Publications and source records attributed to Takeuchi, R. F..

5 recordsLinked to original sources

bioRxiv2025

Thalamus-cortex interactions drive cell type-specific cortical development in human pluripotent stem cell-derived assembloids

The thalamus plays a pivotal role in the development and function of neural circuits in the cerebral cortex. However, how thalamus-cortex interactions influence human cortical development remains unknown primarily because of the inaccessibility of the human embryonic brain. Here, we demonstrate thalamus-dependent gene expression, circuit organization, and neural activity during corticogenesis using human thalamocortical assembloids (hThCAs). Human cortical and thalamic organoids (hCOs and hThOs) derived from induced pluripotent stem cells exhibited region-specific gene expression and spontaneous neuronal activity. Upon the fusion of these organoids, hThCAs reconstructed reciprocal thalamus-cortex axonal projections and synaptic connections. Transcriptomic analysis revealed thalamus-dependent acceleration of cortical maturation, with upregulation of programs linked to axon development, subplate/cortical plate identity, and activity-regulated genes. Histological analysis showed expanded progenitor pools and increased deep-layer neurons within hThCAs. Wide-field Ca2+ imaging demonstrated that wave-like activity originated in the thalamic region and propagated to the cortical region. Furthermore, two-photon Ca2+ imaging of cortical neurons revealed that synchronous activity emerged exclusively in pyramidal tract (PT) and corticothalamic (CT) neurons, whereas intratelencephalic (IT) neurons remain asynchronous, highlighting cell type-specific circuit integration within hThCAs. These synchronized events were absent in isolated hCOs or in cortico-cortical assembloids, underscoring the specificity of thalamic input. Our findings suggest that diffusible thalamic cues broadly enhance progenitor expansion, while long-range thalamic input organizes cell type-specific synchronous activity. This study demonstrates the thalamus-dependent acquisition of mature cortical phenotypes in a cell type-specific manner in hThCAs, establishing developmental mechanisms linking regional interactions and cell type-specific circuit specification. Thus, hThCAs provide a tractable human platform for dissecting human-specific developmental processes and modeling neurodevelopmental disorders with disrupted thalamocortical communication at the molecular, cellular, and circuit levels. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/681772v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@95b599org.highwire.dtl.DTLVardef@c56085org.highwire.dtl.DTLVardef@43df08org.highwire.dtl.DTLVardef@1e7c4ed_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIhThCAs recapitulate the developmental sequence of reciprocal projections with synapses. C_LIO_LIhThCA cortical transcriptomes resemble the late fetal human cortex. C_LIO_LIThalamic paracrine signals promote progenitor expansion and cortical cytoarchitecture. C_LIO_LIWave-like activity originates in the thalamus and propagates across the cortex. C_LIO_LIThalamic input drives cell type-specific synchronization and circuit integration. C_LI

neuroscience↗

bioRxiv2024

Conversion of silent synapses to AMPA receptor-mediated functional synapses in human cortical organoids

Despite the crucial role of synaptic connections and neural activity in the development and organization of cortical circuits, the mechanisms underlying the formation of functional synaptic connections in the developing human cerebral cortex remain unclear. We investigated the development of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic transmission using human cortical organoids (hCOs) derived from induced pluripotent stem cells. Two-photon Ca2 imaging revealed an increase in the frequency and amplitude of spontaneous activity in hCOs on day 80 compared to day 50. Additionally, spontaneous neural activity in late-stage hCOs, but not in early-stage hCOs, was blocked by N-methyl-D-aspartate receptor (NMDAR) and AMPAR antagonists. However, transsynaptic circuit tracing with G-deleted rabies viral vectors indicated a similar number of synaptic connections in early- and late-stage hCOs. Notably, chemical labeling demonstrated a significant increase in AMPAR expression on the postsynaptic membrane and colocalization with NMDAR in late-stage hCOs. These results suggest that hCOs progressively organize excitatory synaptic transmission, concurrent with the transition from silent synapses lacking AMPARs to functional synapses containing NMDARs and AMPARs. This in vitro model of human cortical circuits derived from induced pluripotent stem cells reflects the developmental programs underlying physiological transitions, providing valuable insights into human corticogenesis and neurodevelopmental disorders. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/629885v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1432b6dorg.highwire.dtl.DTLVardef@d8350borg.highwire.dtl.DTLVardef@8273f8org.highwire.dtl.DTLVardef@8bbabd_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

YORU: social behavior detection based on user-defined animal appearance using deep learning

The creation of tools using deep learning methodologies for animal behavior analysis has revolutionized neuroethology. They allow researchers to analyze animal behaviors and reveal causal relationships between specific neural circuits and behaviors. However, the application of such annotation/manipulation systems to social behaviors, in which multiple individuals interact dynamically, remains challenging. Here, we applied an object detection algorithm to classify animal social behaviors. Our system, packaged as "YORU" (Your Optimal Recognition Utility), classifies animal behaviors, including social behaviors, based on the shape of the animal as a "behavior object". It successfully classified several types of social behaviors ranging from vertebrates to insects. We also integrated a closed-loop control system for operating optogenetic devices into the YORU package. YORU enables real-time delivery of photostimulation feedback to specific individuals during specific behaviors, even when multiple individuals are close together. We hope that the YORU system will accelerate the understanding of the neural basis of social behaviors.

neuroscience↗

bioRxiv2023

Modeling the marmoset brain using embryonic stem cell-derived cerebral assembloids

Studying the non-human primate (NHP) brain is required for the translation of rodent research to humans, but remains a challenge for molecular, cellular, and circuit-level analyses in the NHP brain due to the lack of in vitro NHP brain system. Here, we report an in vitro NHP cerebral model using marmoset (Callithrix jacchus) embryonic stem cell-derived cerebral assembloids (CAs) that recapitulate inhibitory neuron migration and cortical network activity. Cortical organoids (COs) and ganglionic eminence organoids (GEOs) were induced from cjESCs and fused to generate CAs. GEO cells expressing the inhibitory neuron marker LHX6 migrated toward the cortical side of CAs. COs developed their neural activity from a synchronized pattern to an unsynchronized pattern as COs matured. CAs showed mature neural activity with an unsynchronized pattern. The marmoset assembloid system will provide an in vitro platform for the NHP neurobiology and facilitate translation into humans in neuroscience research, regenerative medicine, and drug discovery.

neuroscience↗

bioRxiv2022

Posteromedial cortical networks encode visuomotor prediction errors.

Predicting future events based on internal models is essential for animal survival. Predictive coding postulates that errors between prediction and observation in lower-order areas update predictions in higher-order areas through the hierarchy. However, it is unclear how predictive coding is implemented in the hierarchy of the brain. Herein, we report the neural mechanism of the hierarchical processing and transmission of bottom-up prediction error signals in the mouse cortex. Ca2+ imaging and electrophysiological recording in virtual reality revealed responses to visuomotor mismatches in the retrosplenial, dorsal visual, and anterior cingulate cortex. These mismatch responses were attenuated when mismatches became predictable through experience. Optogenetic inhibition of bottom-up signals reduced a behavioral indicator for prediction errors. Moreover, cellular-level mismatch responses were modeled by Bayesian inference using a state-space model. This study demonstrates hierarchical circuit organization underlying prediction error propagation, advancing the understanding of predictive coding in sensory perception and learning in the brain. O_FIG O_LINKSMALLFIG WIDTH=188 HEIGHT=200 SRC="FIGDIR/small/504075v2_ufig1.gif" ALT="Figure 1"> View larger version (82K): org.highwire.dtl.DTLVardef@1f03960org.highwire.dtl.DTLVardef@46df08org.highwire.dtl.DTLVardef@dc97ccorg.highwire.dtl.DTLVardef@7200ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗