Neural Circuits on a Chip

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.

Brain-Derived Neurotrophic Factor (BDNF) Preserves the Functional Integrity of Neural Networks in the β-Amyloidopathy Model in vitro

“…A single neural network in the native brain is extremely difficult to study and cannot be examined in a comprehensive manner at this time. Primary hippocampal cultures are considered an adequate biological model that allows the study of individual cellular and network reactions under stress and the effects of neuroprotectants in a chronic experiment with the possibility of multiple measurements of neural network activity ( Johnstone et al, 2010 ; Vedunova et al, 2015 ; Hasan and Berdichevsky, 2016 ). To investigate the changes in functional neural network activity caused by AD development, we used a protocol for creating primary neuronal cultures obtained from 5xFAD murine embryos.…”

Characterization of in vitro neural functional connectivity on a neurofluidic device

“…From an experimental perspective, dissociated neuronal cultures are usually used as models to the human brain to reconstruct the brain circuitry in vitro . To record electrophysiological signal of these neural cultures, as well as to exert stimulation on target neuronal networks, a variety of planar microelectrode arrays (MEAs) have been intensively used in combination with many microdevices containing neuronal cultures . With the maturation of microfluidic technology, microfluidic devices have gained increasing attention as an ideal platform coupled with MEAs for engineered neural network study.…”

Organ-On-A-Chip in vitro Models of the Brain and the Blood-Brain Barrier and Their Value to Study the Microbiota-Gut-Brain Axis in Neurodegeneration

“…For instance, co-cultures have supported the study of physical communication between cells Facci, 2012, 2018), Transwell R permeable supports have been used to investigate direct cellular communication in the absence of physical contact and conditioned medium has allowed to assess cell interactions in the absence of physical contact by examining the biochemical factors released (Yoshida et al, 1995;Lin et al, 2016). 3D cultures have contributed to address innovative treatments and enhance clinical translation (Shamir and Ewald, 2014;Hopkins et al, 2015;Hasan and Berdichevsky, 2016). For instance, Tang-Schomer et al (2014) have modeled brain cortical architecture and reproduced the compartmentalization of gray and white matter by coupling adhesive-free, concentric silk protein-based porous layers and a collagen gel to support 3D axon connections.…”