Engineered neural circuits for modeling brain physiology and neuropathology

The neural circuits of the central nervous system are the regulatory pathways for feeling, motion control, learning, and memory, and their dysfunction is closely related to various neurodegenerative diseases. Despite the growing demand for the unraveling of the physiology and functional connectivity of the neural circuits, their fundamental investigation is hampered because of the inability to access the components of neural circuits and the complex microenvironment. As an alternative approach, in vitro human neural circuits show principles of in vivo human neuronal circuit function. They allow access to the cellular compartment and permit real-time monitoring of neural circuits. In this review, we summarize recent advances in reconstituted in vitro neural circuits using engineering techniques. To this end, we provide an overview of the fabrication techniques and methods for stimulation and measurement of in vitro neural circuits. Subsequently, representative examples of in vitro neural circuits are reviewed with a particular focus on the recapitulation of structures and functions observed in vivo, and we summarize their application in the study of various brain diseases. We believe that the in vitro neural circuits can help neuroscience and the neuropharmacology. Statement of significance: Despite the growing demand to unravel the physiology and functional connectivity of the neural circuits, the studies on the in vivo neural circuits are frequently limited due to the poor accessibility. Furthermore, single neuron-based analysis has an inherent limitation in that it does not reflect the full spectrum of the neural circuit physiology. As an alternative approach, in vitro engineered neural circuit models have arisen because they can recapitulate the structural and functional characteristics of in vivo neural circuits. These in vitro neural circuits allow the mimicking of dysregulation of the neural circuits, including neurodegenerative diseases and traumatic brain injury. Emerging in vitro engineered neural circuits will provide a better understanding of the (patho-)physiology of neural circuits.