AI Insight
Researchers developed INFORM, a flexible multimodal neural interface that wraps around brain organoids to simultaneously record electrical activity, perform calcium imaging, deliver targeted stimulation, and apply chemical interventions. The technology maintained stable recordings for over a year and detected activity on more than 90% of recording channels, enabling the identification of discrete functional subnetworks within organoids and between fused assembloids. Using neurotransmitter blockade experiments, the team provided direct functional evidence of inhibitory GABAergic signaling in cortical organoids, demonstrating the presence of excitatory-inhibitory circuit balance.
Why it matters
This platform enables unprecedented single-cell resolution mapping of neural circuits in organoids, providing a powerful tool for studying brain development and neurological disorders characterized by excitatory-inhibitory imbalances, such as epilepsy, autism spectrum disorder, and Alzheimer's disease. The long-term stability and multimodal capabilities could accelerate drug screening and disease modeling efforts.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
The balance between excitatory and inhibitory (E/I) neurons is fundamental to cortical function, and its disruption underlies a wide range of neurological disorders, including epilepsy, Alzheimers disease and autism spectrum disorder. Cortical organoids offer a promising model to study this balance, as they recapitulate key features of brain development, including the emergence of E/I circuitry. However, no existing technology can simultaneously resolve neuronal identity, spatial organization, and dynamic network activity within intact organoids, limiting precise interrogation of E/I circuit function. Here, we report INFORM, an INtegrated Flexible Organoid Recording Multimodal neural interface that conformally wraps organoids of any size and shape, enabling long-term recordings over 371 days with above 90% of channels detecting spikes. INFORM interface combines four distinct modalities; electrophysiology, two-photon calcium imaging, targeted electrical microstimulation, and chemical intervention to monitor and modulate neural activity across multiple spatial and temporal scales spanning from action potentials from single neurons to synchronized bursts from large-scale populations. Such high-resolution interrogation enables probing of emergence of functional connectivity in fusing assembloids and resolves spatially discrete functional subnetworks that can be selectively recruited and modulated by INFORM. Neurotransmission blockade confirms that stimulus-evoked suppression of neuronal spiking is mediated by GABAergic inputs providing direct functional evidence of the presence of inhibitory signaling in organoids. This work allows single-cell dissection of functional networks in brain organoids, providing a powerful platform for modelling and studying cortical development, neurological diseases, and the E/I imbalances underlying circuit dysfunction.