Advanced Technologies for Local Neural Circuits in the Cerebral Cortex.

Masaaki Endo,Hisato Maruoka,Shigeo Okabe

doi:10.3389/fnana.2021.757499

Abstract

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.

Highlights

The neural network in the brain can be considered an integrated system consisting of many local circuits with particular functions
This study demonstrates the potential of retrospective tracing in developmental biology and accelerated the development of similar CRISPR/Cas9 systembased cell lineage tracing methods (Perli et al, 2016; Shipman et al, 2016; Kalhor et al, 2017; Alemany et al, 2018; Spanjaard et al, 2018; Garcia-Marques et al, 2020)
It should be emphasized that there are a number of new studies applying innovative technologies to neural circuit analysis; spatial transcriptome technology with optical clearing methods (Wang et al, 2018), a functional connectomics technology combined in vivo two-photon calcium imaging, and electron microscopy (Bock et al, 2011; Briggman et al, 2011; Lee et al, 2016; Scholl et al, 2021)

Summary

Introduction

The neural network in the brain can be considered an integrated system consisting of many local circuits with particular functions. How neurons within a local neural circuit follow the principles of connectivity based on their cell type, morphology, gene expression, and neural activity. Progress in neural circuit analysis requires integration with multiple novel technologies based on imaging, tissue processing, transcription analysis, and cell lineage tracing.

Results

Conclusion