“Brains on a chip”: Towards engineered neural networks

Aebersold, Mathias J.; Dermutz, Harald; Forró, Csaba; Weydert, Serge; Thompson-Steckel, Greta; Vörös, János; Demkó, László

doi:10.1016/j.trac.2016.01.025

Cited by 72 publications

(77 citation statements)

References 98 publications

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“…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 .…”

Section: Introductionmentioning

confidence: 99%

Characterization of in vitro neural functional connectivity on a neurofluidic device

Shen

Wang

et al. 2019

Electrophoresis

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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.

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Section: Introductionmentioning

confidence: 99%

Characterization of in vitro neural functional connectivity on a neurofluidic device

Shen

Wang

et al. 2019

Electrophoresis

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show abstract

Section: Introductionmentioning

confidence: 99%

“…Considerable efforts have been directed to develop in vitro culture strategies and tools to realistically reproduce the neuron development and growth while governing the complexity of neural population organization (4), (5), (6), (7), (8). The goal is to gain a deeper understanding of and control over the interaction of single building blocks concurring to brain complexity and to disentangle the relationship between structural organization and functional behavior (4), (5),(6), (7), (8), (9), (10). The potential applications are certainly manifold and versatile, ranging from the comprehension of the network communication and crosstalk between different types of neurons, to the realization of alternatives for animal models and brain slices to study neural disorders or the development of drug testing platforms in brain-on-chip approaches (4), (5),(6), (7), (8).…”

Section: Introductionmentioning

confidence: 99%

Neuronal Cells Confinement by Micropatterned Cluster-Assembled Dots with Mechanotransductive Nanotopography

Schulte

Lamanna

Moro

et al. 2018

Preprint

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The in vitro fabrication of neural networks able to simulate brain circuits and to maintain their native connectivity is of strategic importance to gain a deep understanding of neural circuit physiology and brain natural computational algorithm(s). This would also enable a wide-range of applications including the development of efficient brain-on-chip devices or brain-computer interfaces. Chemical and mechanotransductive cues cooperate to promote proper development and functioning of neural networks. Since the 80's, controlled growth of mammalian neuronal cells on micrometric patterned chemical cues with the development of synaptic connections and electrical activity has been reported, however the role of mechanotransductive signaling on the growth/organization of neural networks has not been investigated so far. Here we report the fabrication and characterization of patterned substrates for neuronal culture with a controlled structure both at the nano-and microscale suitable for the selective adhesion of neuronal cells. Nanostructured micrometric dots were patterned on passivated cell-repellent glass substrates by supersonic cluster beam deposition of zirconia nanoparticles through stencil masks. Cluster-assembled nanostructured zirconia surfaces are characterized by nanotopographical features that can direct the maturation of neural networks by mechanotransductive signaling. Our approach produces a controlled microscale pattern of adhesive areas with predetermined nanoscale morphology. We have validated these micropatterned substrates using a neuronal cell line (PC12 cells) and cultured hippocampal neurons. While cells have been uniformly plated on the substrates, they adhered only on the nanostructured zirconia regions, remaining effectively confined inside the nanostructured dots on which they were found to grow, move and differentiate.

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“…Unraveling how billions of nerve cellsi nt he humanb rain work together and carry out their functions, which range from processing sensory signals to storingi nformation, is one of the key challenges of this century. [1] The brain is predominately studied either as aw hole in at op-down fashion or from the bottom up at the level of single cells and small networks. Basic functions of the brain, such as perception, processing, and the storage of information, are carriedo ut by networks of tens to hundreds of cells.…”

Section: Introductionmentioning

confidence: 99%

“…Microfluidic devices have given researchers the possibility to controlt he positiono fn eurons and how they interconnect,a nd to manipulate individual compartments. [1,[37][38][39] For example, am icrofluidic chip was used to record and chemically stimulate brain tissue slices simultaneously, [40] and an on-chip fluid delivery system was used to apply neurotransmitters locally to ap atterned network of neurons and also perform patch-clamp recordings. [41] These microfluidic systems are well suited for automatized measurements.…”

Section: Introductionmentioning

confidence: 99%

Local Chemical Stimulation of Neurons with the Fluidic Force Microscope (FluidFM)

et al. 2017

Self Cite

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Physiological communication between neurons is dependent on the exchange of neurotransmitters at the synapses. Although this chemical signal transmission targets specific receptors and allows for subtle adaptation of the action potential, in vitro neuroscience typically relies on electrical currents and potentials to stimulate neurons. The electric stimulus is unspecific and the confinement of the stimuli within the media is technically difficult to control and introduces large artifacts in electric recordings of the activity. Here, we present a local chemical stimulation platform that resembles in vivo physiological conditions and can be used to target specific receptors of synapses. Neurotransmitters were dispensed using the force-controlled fluidic force microscope (FluidFM) nanopipette, which provides exact positioning and precise liquid delivery. We show that controlled release of the excitatory neurotransmitter glutamate induces spiking activity in primary rat hippocampal neurons, as measured by concurrent electrical and optical recordings using a microelectrode array and a calcium-sensitive dye, respectively. Furthermore, we characterized the glutamate dose response of neurons by applying stimulation pulses of glutamate with concentrations from 0 to 0.5 mm. This new stimulation approach, which combines FluidFM for gentle and precise positioning with a microelectrode array read-out, makes it possible to modulate the activity of individual neurons chemically and simultaneously record their induced activity across the entire neuronal network. The presented platform not only offers a more physiological alternative compared with electrical stimulation, but also provides the possibility to study the effects of the local application of neuromodulators and other drugs.

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“Brains on a chip”: Towards engineered neural networks

Cited by 72 publications

References 98 publications

Characterization of in vitro neural functional connectivity on a neurofluidic device

Characterization of in vitro neural functional connectivity on a neurofluidic device

Neuronal Cells Confinement by Micropatterned Cluster-Assembled Dots with Mechanotransductive Nanotopography

Local Chemical Stimulation of Neurons with the Fluidic Force Microscope (FluidFM)

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