Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Functional neuronal circuitry and oscillatory dynamics in human brain organoids

ABSTRACT: Human brain organoids replicate much of the cellular diversity and developmental anatomy of the human brain. However, the physiology of neuronal circuits within organoids remains under-explored. With high-density CMOS microelectrode arrays and shank electrodes, we captured spontaneous extracellular activity from brain organoids derived from human induced pluripotent stem cells. We inferred functional connectivity from spike timing, revealing a large number of weak connections within a skeleton of significantly fewer strong connections. A benzodiazepine increased the uniformity of firing patterns and decreased the relative fraction of weakly connected edges. Our analysis of the local field potential demonstrate that brain organoids contain neuronal assemblies of sufficient size and functional connectivity to co-activate and generate field potentials from their collective transmembrane currents that phase-lock to spiking activity. These results point to the potential of brain organoids for the study of neuropsychiatric diseases, drug action, and the effects of external stimuli upon neuronal networks.

ORGANISM(S): Homo sapiens

PROVIDER: GSE207749 | GEO | 2022/07/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The injury environment critically influences the brain-wide input connectome of transplanted neurons

Project description:Cell transplantation is a promising approach for reconstruction of neuronal circuits after brain damage. Transplanted neurons integrate with remarkable specificity into circuitries of the mouse cerebral cortex affected by neuronal ablation. However, it remains unclear how neurons perform in a local environment undergoing reactive gliosis, inflammation, macrophage infiltration and scar formation, as in brain trauma. To elucidate this, we transplanted cells from the embryonic murine cerebral cortex into stab-injured, inflamed-only, or intact cortex of adult mice. Brain-wide quantitative connectomics unraveled graft inputs from correct regions across the brain in all conditions, with pronounced quantitative differences: scarce in intact or inflamed brain, versus exuberant after trauma. In the latter, excessive synapse pruning follows the initial overshoot of connectivity resulting in only a few input connections left. Proteomic profiling identifies candidate molecules involved in the synaptic yield, a pivotal parameter to tailor for functional restoration of neuronal circuits.

2022-08-12 | PXD023660 | Pride

Microglia and brain organoids

Project description:iPSC-derived microglia export cholesterol to neuronal cells in human brain organoids and promote their maturation

2023-05-19 | PXD042344 | JPOST Repository

Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits

Project description:How neuronal connections are established and organized in functional networks determines brain function. In the mouse cerebral cortex, different classes of GABAergic interneurons exhibit specific connectivity patterns that underlie their ability to shape temporal dynamics and information processing. Much progress has been made parsing interneuron diversity, yet the molecular mechanisms by which interneuron subtype-specific connectivity motifs emerge remain unclear. Here we investigate transcriptional dynamics in different classes of interneurons during the formation of cortical inhibitory circuits. We found that whether the interneurons synapse with pyramidal neurons on their dendrites, soma, or axon initial segment is determined by synaptic molecules that are expressed in a subtype-specific manner. Thus cell-specific molecular programs that unfold during early postnatal development underlie the connectivity patterns of cortical interneurons.

2019-01-25 | GSE120161 | GEO

Advanced Complexity and Short-Term Plasticity of Neural Activity in Reciprocally Connected Human Cerebral Organoids

Project description:An inter-regional cortical tract is one of the most fundamental architectural motifs that integrates neural circuits to orchestrate and generate complex functions of the human brain. To understand the mechanistic significance of inter-regional projections on development of neural circuits, we investigated an in vitro neural tissue model for inter-regional connections, in which two cerebral organoids are connected with a bundle of reciprocally extended axons. The connected organoids produced more complex and intense oscillatory activity than conventional or directly fused cerebral organoids, suggesting the inter-organoid axonal connections enhance and support the complex network activity. In addition, optogenetic stimulation of the inter-organoid axon bundles could entrain the activity of the organoids and induce robust plasticity of the macroscopic circuit. These results demonstrated that the projection axons could serve as a structural hub that boosts functionality of the organoid-circuits. This model could contribute to further investigation on development and functions of macroscopic neuronal circuits in vitro.

2024-02-22 | GSE190729 | GEO

Secretomic effects of amyloid beta peptides on Alzheimer’s disease related proteins in differentiated SH-SY5Y neuroblastoma cell

Project description:Alzheimer’s disease (AD) is a neurodegenerative disease that causes physical damage to neuronal connections, leading to brain atrophy. This disruption of synaptic connections results in mild to severe cognitive impairments. Unfortunately, no effective treatment is currently known to prevent or reverse the symptoms of AD. The aim of this study was to investigate the effects of 3 synthetic peptides on an AD in vitro model represented by differentiated SH-SY5Y neuroblastoma cells exposed to retinoic acid (RA) and brain-derived neurotrophic factor (BDNF).

2024-01-03 | PXD045244 | JPOST Repository

Klotho inhibits neuronal senescence in human brain organoids

Project description:Klotho inhibits neuronal senescence in human brain organoids

| PRJNA720649 | ENA

Genome-wide profiling of the activity-dependent hippocampal transcriptome

Project description:Activity-dependent gene expression is central for sculpting neuronal connectivity in the brain. Despite the importance for synaptic plasticity, a comprehensive analysis of the temporal changes in the transcriptomic response to neuronal activity is lacking. In a genome wide survey we identified genes that were induced at 1, 4, 8, or 24 hours following neuronal activity in the hippocampus. 3 month old male mice were injected with kainic acid or isotonic saline solution. Animals were sacrificed by cervical luxation 1, 2, 4, 8, or 24 h after onset of the first seizure, and RNA was extracted from the hippocampal region.

2013-10-23 | E-GEOD-49030 | biostudies-arrayexpress

Complementary Expression of Immunoglobulin Superfamily Ligands and Receptors in Synaptic Pairs in the Drosophila Visual System

Project description:Purpose: Information processing in the brain relies on precise patterns of synapses between neurons. The molecular mechanisms by which this specificity is achieved remains elusive. In the medulla of the Drosophila visual system, different neurons form synaptic connections in different layers. Methods: we developed methods to purify seven neuronal cell types (R7, R8 and L1-L5 neurons) using Fluorescence Activated Cell Sorting. Results: we show that neurons with different synaptic specificities express unique combinations of mRNAs encoding hundreds of cell surface and secreted proteins. Using RNA sequencing and MiMIC-based protein tagging, we demonstrate that 21 paralogs of the Dpr family, a subclass of Immunoglobulin (Ig)-domain containing proteins, are expressed in unique combinations in homologous neurons with different layer-specific synaptic connections. Dpr interacting proteins (DIPs), comprising nine paralogs of another subclass of Ig superfamily proteins, are expressed in a complementary layer-specific fashion in a subset of synaptic partners. We propose that pairs of Dpr/DIP paralogs contribute to layer-specific patterns of synaptic connectivity. Conclusions: This complexity is mirrored by the complexity of the cell surface and secreted molecules expressed by each of the R cell and lamina neurons profiled in this study. How this complexity contributes to specificity remains elusive, but the convergence of improved histological, genetic and molecular tools promises to provide important insights into the molecular recognition strategies controlling synaptic specificity. We chose 7 time points for RNA-seq analysis of R cells during pupal development corresponding to 24, 35, 40, 45, 53, 65 and 96 hrs after pupal formation (APF).

2015-12-17 | E-GEOD-68235 | biostudies-arrayexpress

Genome-wide profiling of the activity-dependent hippocampal transcriptome

2013-10-23 | GSE49030 | GEO

Fusion of Human Brain Organoids Assembles Bidirectional Connectivity Between Thalamus and Cortex

Project description:Fusion of Human Brain Organoids Assembles Bidirectional Connectivity Between Thalamus and Cortex

| PRJNA504661 | ENA