Thalamocortical axons regulate neurogenesis and laminar fates in early sensory cortex

Nakagawa, Yasushi; Monko, Timothy; Rebertus, Jaclyn; Stolley, Jeff; Salton, Stephen R.J.

doi:10.1101/2021.06.16.448668

Cited by 3 publications

(2 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, glutamate release from thalamocortical afferents promotes morphological development of layer neurons in the postnatal primary somatosensory cortex (Narboux-Nême et al, 2012;Li et al, 2013). These cell identity oriented molecular cues culminate in laminar and areal fates, as thalamocortical afferents (Dehay et al, 1991(Dehay et al, , 2001Reillo et al, 2011) can also instruct specification toward sensory areal identity in neocortical postmitotic neurons (Chou et al, 2013;Vue et al, 2013;Pouchelon et al, 2014) and regulate neurogenesis and laminar fates in sensory cortex (Monko et al, 2021). Rodent studies have therefore improved our understanding of thalamocortical circuit assembly and refinement across brain regions.…”

Section: The Mechanisms Of Cortical Arealization Stem From Both Intrinsic and Extrinsic Signalingmentioning

confidence: 99%

Cortical Cartography: Mapping Arealization Using Single-Cell Omics Technology

Nano

Nguyen

Mil

et al. 2021

Front. Neural Circuits

View full text Add to dashboard Cite

The cerebral cortex derives its cognitive power from a modular network of specialized areas processing a multitude of information. The assembly and organization of these regions is vital for human behavior and perception, as evidenced by the prevalence of area-specific phenotypes that manifest in neurodevelopmental and psychiatric disorders. Generations of scientists have examined the architecture of the human cortex, but efforts to capture the gene networks which drive arealization have been hampered by the lack of tractable models of human neurodevelopment. Advancements in “omics” technologies, imaging, and computational power have enabled exciting breakthroughs into the molecular and structural characteristics of cortical areas, including transcriptomic, epigenomic, metabolomic, and proteomic profiles of mammalian models. Here we review the single-omics atlases that have shaped our current understanding of cortical areas, and their potential to fuel a new era of multi-omic single-cell endeavors to interrogate both the developing and adult human cortex.

show abstract

Section: The Mechanisms Of Cortical Arealization Stem From Both Intrinsic and Extrinsic Signalingmentioning

confidence: 99%

Cortical Cartography: Mapping Arealization Using Single-Cell Omics Technology

Nano

Nguyen

Mil

et al. 2021

Front. Neural Circuits

View full text Add to dashboard Cite

show abstract

“…In the developing brain, thalamic inputs mold the laminar, columnar, and functional organization of the cortex. 88,89 Similarly, more mature thalamic projections might promote organizational maturation in hCOs, and more organized TC assembloids might better model the diversity of synaptic plasticity mechanisms observed across TC sensory pathways. Assembloids modeling other brain structures [90][91][92] (or synaptic targets outside the brain) 93 might also elucidate mechanisms that differ between neural circuits.…”

Section: Discussionmentioning

confidence: 99%

Synaptic plasticity in human thalamocortical assembloids

Patton,

Thomas,

Bayazitov

et al. 2024

Preprint

View full text Add to dashboard Cite

SUMMARYSynaptic 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 most cells in mature 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.HighlightsHuman thalamic organoids consist of mostly glutamatergic projection neurons.Thalamocortical assembloids form reciprocal glutamatergic synapses.Synapses are functional and undergo short-term plasticity resembling animal models.Long-term potentiation and depression reveal mechanisms distinct from rodents.eTOCHuman organoids are often used to model diseases with synaptic pathology; however, few studies have examined synaptic function via single-cell or single-synapse recordings. Patton et al. fused human thalamic and cortical organoids into assembloids to examine synaptic transmission and short- and long-term synaptic plasticity in human thalamocortical and corticothalamic circuits.GRAPHICAL ABSTRACT

show abstract

Evaluation of advances in cortical development using model systems

Nano

Bhaduri

2022

Developmental Neurobiology

View full text Add to dashboard Cite

Compared with that of even the closest primates, the human cortex displays a high degree of specialization and expansion that largely emerges developmentally. Although decades of research in the mouse and other model systems has revealed core tenets of cortical development that are well preserved across mammalian species, small deviations in transcription factor expression, novel cell types in primates and/or humans, and unique cortical architecture distinguish the human cortex. Importantly, many of the genes and signaling pathways thought to drive human‐specific cortical expansion also leave the brain vulnerable to disease, as the misregulation of these factors is highly correlated with neurodevelopmental and neuropsychiatric disorders. However, creating a comprehensive understanding of human‐specific cognition and disease remains challenging. Here, we review key stages of cortical development and highlight known or possible differences between model systems and the developing human brain. By identifying the developmental trajectories that may facilitate uniquely human traits, we highlight open questions in need of approaches to examine these processes in a human context and reveal translatable insights into human developmental disorders.

show abstract

Thalamocortical axons regulate neurogenesis and laminar fates in early sensory cortex

Cited by 3 publications

References 73 publications

Cortical Cartography: Mapping Arealization Using Single-Cell Omics Technology

Cortical Cartography: Mapping Arealization Using Single-Cell Omics Technology

Synaptic plasticity in human thalamocortical assembloids

Evaluation of advances in cortical development using model systems

Contact Info

Product

Resources

About