Advanced Technologies for Local Neural Circuits in the Cerebral Cortex

Abstract

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The neural network in the brain can be viewed as an integrated system assembled from a large number of local neural circuits specialized for particular brain functions. Activities of neurons in local neural circuits are thought to be organized both spatially and temporally under the rules optimized for their roles in information processing. It is well perceived that different areas of the mammalian neocortex have specific cognitive functions and distinct computational properties. However, the organizational principles of the local neural circuits in different cortical regions have not yet been clarified. Therefore, new research principles and related neuro-technologies that enable efficient and precise recording of large-scale neuronal activities and synaptic connections are necessary. Innovative technologies for structural analysis, including tissue clearing and expansion microscopy, have enabled super resolution imaging of the neural circuits containing thousands of neurons at a single synapse resolution. The imaging resolution and volume achieved by new technologies are beyond the limits of conventional light or electron microscopic methods. Progress in genome editing and related technologies has made it possible to label and manipulate specific cell types and discriminate activities of multiple cell types. These technologies will provide a breakthrough for multiscale analysis of the structure and function of local neural circuits. This review summarizes the basic concepts and practical applications of the emerging technologies and new insight into local neural circuits obtained by these technologies.

Keywords

• local neural circuit
• optical clearing
• expansion microscopy
• volumetric electron microscopy
• spatial transcriptomics
• lineage tracing