Abstract

Neural circuits are responsible for the brain’s ability to process and store information. Reductionist approaches to understanding the brain include isolation of individual neurons for detailed characterization. When maintained in vitro for several days or weeks, dissociated neurons self-assemble into randomly connected networks that produce synchronized activity and are capable of learning. This review focuses on efforts to control neuronal connectivity in vitro and construct living neural circuits of increasing complexity and precision. Microfabrication-based methods have been developed to guide network self-assembly, accomplishing control over in vitro circuit size and connectivity. The ability to control neural connectivity and synchronized activity led to the implementation of logic functions using living neurons. Techniques to construct and control three-dimensional circuits have also been established. Advances in multiple electrode arrays as well as genetically encoded, optical activity sensors and transducers enabled highly specific interfaces to circuits composed of thousands of neurons. Further advances in on-chip neural circuits may lead to better understanding of the brain.

Highlights

  • Neural circuits are responsible for the brain’s ability to process sensory information, recall memories, experience emotions, learn, and control the muscles of the body

  • Major approaches to the study of neural circuits include the examination of circuits in the intact brain in the context of relevant behavior as well as reductionist approaches where neural circuits or individual neurons are isolated from the rest of the brain for detailed electrophysiological and biochemical characterization

  • Researchers hypothesized that the direction of axon growth and dendrite growth could be controlled by patterning the culture substrate

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Summary

Introduction

Neural circuits are responsible for the brain’s ability to process sensory information, recall memories, experience emotions, learn, and control the muscles of the body. Isolation can be accomplished by dissecting a slice of the brain that contains a circuit of interest, or dissociating the brain into individual neurons and allowing these neurons to form randomly connected networks in vitro. Advances in microfabrication and neuron culture techniques made it possible to control connectivity between dissociated neurons or slices. It is possible to envision building living neural circuits of increasing complexity and precision to understand the brain’s ability to process and store information. Recent efforts toward this goal, including methods of circuit construction, stimulation, and detection of neural activity, and the achievement of pre-designed circuit functions are the subject of this review

Dissociated Neural Cultures
Patterned Networks
Structured Organotypic and 3D Dissociated Neural Cultures
Interfaces to Neural Circuits
Electrical Interfaces
Optical Interfaces
Findings
Conclusions
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