Formation of one-way-structured cultured neuronal networks in microfluidic devices combining with micropatterning techniques

Takayama, Yoichiro; Kotake, Naoki; Haga, Tatsuya; Suzuki, Takafumi; Mabuchi, Kunihiko

doi:10.1016/j.jbiosc.2012.02.011

Cited by 29 publications

(19 citation statements)

References 15 publications

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“…108 Using surface patterning and fluidic resistance, axons can be preferentially separated from the dendrites, hence creating a model to study axonal growth, injury and recovery. 45,109,110 Nguyen et al utilized a vacuum-supplemented microfluidic channel array that models an array of 25 micropipette tips to apply mechanical tension to seeded neurons.…”

Section: Micro-technologiesmentioning

confidence: 99%

Acute and Chronic Neural Stimulation via Mechano-Sensitive Ion Channels

Tay

2018

Springer Theses

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Neural stimulation techniques for eliciting calcium influx can elucidate the physiological roles of specific neural populations. To overcome some of the limitations of existing techniques such as poor specificity and noxious effects of heat, I developed a technology for non-invasive control of neural activities using magnetic forces and magnetic nanoparticles (MNPs) which offer deep tissue penetration and controllable dosage. Extensive investigations with different neurotoxins and experimental conditions support that the mechanism of magnetic stimulation that involves membrane-bound MNPs transducing magnetic forces into mechanical stretching of the cell membrane to enhance the opening probability of mechano-sensitive N-type calcium ion channels to induce calcium influx.Making use of the ability of neural networks to actively regulate their ratio of excitatory to inhibitory ion channel/receptor, I also performed chronic magnetic stimulation on fragile X iii syndrome (FXS) model neural networks. We found that chronic magnetic stimulation reduced the density of N-type calcium ion channels whose expression is increased in FXS. This technique demonstrates the potential of using bio-magnetic/mechanical forces to modulate expressions of mechano-sensitive ion channels where they are over-expressed in diseases such as abnormal nociception.Nonetheless, there are still a few areas where the technique can be improved. Firstly, it is the use of MNPs with more uniform properties to have greater control on magnetic stimulations.Secondly, the technique needs to be useful for in vivo studies. Therefore, I started researching on magnetotactic bacteria (MTB) which produce biological MNPs with superior properties such as uniform sizes and highly homogenous magnetic properties with the goal of harvesting MNPs from them.MTB, however, grow extremely slowly and the number of MNPs produced/bacterium is low. One way to overcome this problem is to evolve MTB over-producers of MNPs but this strategy is constrained by the absence of a selection platform that is quantitative and offer high throughput. To overcome this problem, I combined random chemical mutagenesis and selection using a magnetic ratcheting platform to generate and isolate MTB over-producers that produce twice as many MNPs/bacterium after 5 rounds of mutation/selection. I next designed a magnetic microfluidic device and demonstrate as a proof of concept, that it can be coupled to a bioreactor for high throughput microfluidic selection of MTB over-producers.iv

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Section: Micro-technologiesmentioning

confidence: 99%

Acute and Chronic Neural Stimulation via Mechano-Sensitive Ion Channels

Tay

2018

Springer Theses

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“…[10][11][12][13][14] Microcontact printing on surface-modified substrates has been used to immobilize cell adhesive molecules in a micron-scale pattern for the study of neurite growth. 9 The method requires the complicated process of chemical modification.…”

Section: Introductionmentioning

confidence: 99%

“…9 The method requires the complicated process of chemical modification. The use of microfluidic devices for detailed observations of neurites and growth cones using non-fluorescent imaging, such as phase-contrast or differential interference contrast (DIC) microscopy, 11,14 has been impeded by the effects of light refraction from microfluidic structures.…”

Section: Introductionmentioning

confidence: 99%

A Simplified Micropatterning Method for Straight-line Neurite Extension of Cultured Hippocampal Neurons

et al. 2013

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“…To reveal functional interconnections and their changes after stimulation, various methods of mathematical analysis are needed [11,12]. In recent years, development of microfluidic techniques has allowed guiding growth of neurites and forming cultures with required functional connections [13][14][15][16][17][18][19][20]. Connections in which signals propagate in one direction are the most interesting because pre-and postsynaptic cells involved in them are in separate chambers.…”

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confidence: 99%

Study of Stimulus-Induced Plasticity in Neural Networks Cultured in Microfluidic Chips

Gladkov¹,

Колпаков²,

Pigareva³

et al. 2017

Sovrem Tehnol Med

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Dissociated brain cell cultures on microelectrode arrays are widely used to study fundamental mechanisms of information processing and synaptic plasticity. It has been established that high frequency electrical stimulation causes functional changes in neural networks. However, complex and homogeneous morphological structure of cultured brain cell networks presents a significant challenge for further evaluation of the synaptic plasticity at the network level. In this study, we propose a new approach to studying neural network plasticity using microfluidic devices with specially designed channels. Microfluidic chips can guide axons and form neural circuits with two subnetworks connected by synaptic paths in the required direction. To induce synaptic plasticity, high frequency tetanic stimulation by two groups of electrodes located in the area of pre-and postsynaptic neurons was applied. The developed method of potentiation and depression of the required functional connectivity in the neural circuit can be used to further study network effects of synaptic plasticity induced in the local subpopulation of cells.

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Formation of one-way-structured cultured neuronal networks in microfluidic devices combining with micropatterning techniques

Cited by 29 publications

References 15 publications

Acute and Chronic Neural Stimulation via Mechano-Sensitive Ion Channels

Acute and Chronic Neural Stimulation via Mechano-Sensitive Ion Channels

A Simplified Micropatterning Method for Straight-line Neurite Extension of Cultured Hippocampal Neurons

Study of Stimulus-Induced Plasticity in Neural Networks Cultured in Microfluidic Chips

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