Characterization of in vitro neural functional connectivity on a neurofluidic device

Abstract

Understanding the mechanism of functional connectivity in neural system is of great benefit to lot of researches and applications. Microfluidics and microelectrode arrays (MEAs) have been frequently utilized for in vitro neural cultures study. However, there are few studies on the functional connectivity of neural cultures grown on a microfluidic chip. It is intriguing to unveil the influences of microfluidic structures on in vitro neuronal networks from the perspective of functional connectivity. Hence, in the present study, a device was established, which comprised a microfluidic chamber for cell growth and a MEA substrate for recording the electrophysiological response of the neuronal networks. The network topology, neural firing rate, neural bursting rate and network burst frequency were adopted as representative characteristics for neuronal networks analysis. Functional connectivity was estimated by means of cross‐covariance analysis and graph theory. The results demonstrated that the functional connectivity of the in vitro neuronal networks formed in the microchannel has been apparently reinforced, corresponding to improve neuronal network density and increased small‐worldness.

The microbiota‐gut‐brain axis and epilepsy from a multidisciplinary perspective: Clinical evidence and technological solutions for improvement of in vitro preclinical models

“…The micrometric dimension of the channels and the controlled flow velocity led to axonal growth and alignment along the channel direction 199 . This latter phenomenon was also reported by Shen and co‐authors who proposed a neuro fluidic micro‐device showing the influence of microfluidic constrain on the functional neural connectivity, which was measured by an integrated MEA inside the microchamber 184 …”

“…There are some fundamental elements for BoCs design and manufacturing: microchannels, that can be used as neurite growth guide, as scaffolds, or basically to provide perfusion and biochemical gradients; microchambers, to allow spatial separation between different cell types or heterogeneous tissues formation; ECM components for three‐dimensionality representation; electroactive components such as MEAs for stimulation and recording. All those elements are connected to specific functional features as dynamic mechanical stress, mass transport of solutes, analysis of neural electrical activity, and distribution of biochemical cues 183–188 …”

Integrating Biosensors in Organs-on-Chip Devices: A Perspective on Current Strategies to Monitor Microphysiological Systems

“…Once a neural circuit is implemented on chip, the possibility to record the electrical activity of the neuronal populations in real time is an essential requirement to acquire a basic understanding of the network functionality. To this aim, several studies have successfully demonstrated the integration of commercial or custom-made multielectrode arrays (MEAs) within microfluidic chips [ 53 , 133 , 134 , 135 , 136 , 137 , 138 ]. In details, MEAs are composed of a set of microelectrodes typically arranged in a matrix configuration, that enable to record extracellular activity of neuronal populations from multiple sites simultaneously in a noninvasive way [ 139 , 140 , 141 ].…”

An ALE Meta-Analysis of Specific Functional MRI Studies on Subcortical Vascular Cognitive Impairment

“…Resting-state functional magnetic resonance imaging (fMRI) has made it possible for researchers to detect alterations in brain functional networks and local spontaneous neuronal activity, which provides new insight into the pathogenesis of neurological diseases (9). At present, there are three reliable technical means widely used in fMRI, including the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) (10)(11)(12). The ALFF is used to describe spontaneous regional brain activity and ReHo is used to demonstrate the consistency of brain activity (10).…”

“…The ALFF is used to describe spontaneous regional brain activity and ReHo is used to demonstrate the consistency of brain activity ( 10 ). FC reveals whether there is connectivity disruption or compensation in the brain regions ( 12 ). In the field of neuroimaging, the known networks for cognitive impairment include the default mode network (DMN), the executive control network (ECN), and the visual network (VN).…”