Engineered In Vitro Platforms to Probe Neural Circuit Dysfunction in CNS Disorders

Disorders of the central nervous system (CNS) - including neurodegenerative, neurodevelopmental, and neuropsychiatric conditions - arise from complex alterations in neuronal and glial function, synaptic communication, and circuit organization. Despite major advances in molecular neuroscience, how cellular dysfunction develops into aberrant network activity remains poorly understood, and conventional models often fail to reproduce human neural circuitry, cellular diversity, and patient-specific pathophysiology. Meeting this challenge requires new neurotechnologies capable of building and interrogating human neural circuits in vitro.Advances in human induced pluripotent stem cell (iPSC) technology, three-dimensional neural organoids, assembloids, and microphysiological systems are creating sophisticated models of the human nervous system. Their scientific value, however, is unlocked by the engineered technologies used to interface with them - high-density and nanomaterial-based microelectrode arrays, microfluidic and organ-on-chip platforms, biosensors, optogenetic and chemogenetic interfaces, and functional imaging. This convergence of neurobiology with micro- and nanotechnology offers unprecedented opportunities to monitor and manipulate neuronal and glial activity across multiple spatial and temporal scales.The central aim of this Research Topic is to highlight engineered in vitro platforms - and the innovations behind them - that enable quantitative investigation of neural circuit dysfunction in CNS disorders. We emphasize neural-technology advances that go beyond method development to generate genuine change in how researchers monitor, manipulate, and characterize functional neural networks, and that link molecular or cellular pathology to altered circuit dynamics.These platforms will be showcased across neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease and related dementias; neurodevelopmental disorders including autism spectrum disorders and intellectual disability; epilepsy; and neuropsychiatric conditions such as schizophrenia and depression, with a functional-network readout of dysfunctional circuits. Studies of interactions among neurons, astrocytes, microglia, and oligodendrocytes are encouraged where these can be interrogated at the functional network level.We welcome original research, methodological studies, reviews, perspectives, and proof-of-concept studies on:- iPSC-derived neuronal and glial systems- Brain organoids and assembloids- Neural microphysiological and organ-on-chip platforms- High-density, multielectrode, and nanomaterial-based array technologies- Microfluidic systems for reconstructing neural circuits- Advanced electrophysiology- Functional calcium and voltage imaging- Optogenetic and chemogenetic interrogation of in vitro networks- Multimodal integration of electrophysiology and imaging- Computational analysis of network dynamics- Disease modelling and patient-specific neural platforms- Engineered neural systems for pharmacological screening and therapeutic discoveryParticular consideration will be given to studies that move beyond descriptive cellular phenotypes to provide quantitative measurements of network excitability, connectivity, synchronization, oscillatory activity, synaptic transmission, plasticity, and information processing. Contributions addressing reproducibility, standardization, scalability, benchmarking, and translation of advanced in vitro platforms are also encouraged.By bringing together neuroscience, stem-cell biology, bioengineering, electrophysiology, imaging, and computational approaches, this Research Topic defines how next-generation engineered in vitro systems can advance understanding of human neural circuit dysfunction. In line with the section’s focus on the convergence of neurobiology and micro- and nanotechnology, and its relevance to good health and well-being (SDG 3) and innovation and infrastructure (SDG 9), these technologies can bridge molecular mechanisms and systems-level pathology, improve disease modelling, reveal therapeutic targets, and accelerate predictive platforms for CNS drug discovery. Topic editors: Giuseppe Di Giovanni, Teresa Pasqua, Vincenzo Crunelli Source: https://www.frontiersin.org/research-topics/85023/engineered-in-vitro-platforms-to-probe-neural-circuit-dysfunction-in-cns-disorders