A multielectrode microcompartment culture platform for studying signal transduction in the nervous system

Ravula, Surendra K.; McClain, Maxine A.; Wang, Min S.; Glass, Jonathan D.; Frazier, A. Bruno

doi:10.1039/b612684g

Cited by 26 publications

(20 citation statements)

References 34 publications

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“…The devices can be integrated with not only conventional recording technologies such as patch clamp (Berdichevsky et al ., 2010), but also new recording technologies such as multi-electrode arrays (MEAs) (Dworak and Wheeler, 2009; Claverol-Tinturé et al ., 2005, 2007; Ravula et al ., 2006, 2007a, 2007b). The MEA provides an ideal means of recording simultaneously from multiple neurons.…”

Section: Introductionmentioning

confidence: 99%

Propagation of action potential activity in a predefined microtunnel neural network

et al. 2011

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A polydimethylsiloxane (PDMS) microtunnel device with two wells is aligned and attached on top of a multi-electrode-array (MEA). Neurons are grown first in one well and allowed to propagate axons through the tunnels into a second well. After ten days cells are plated in the second well, with much lower likelihood of extending axons back to the first well, with the intent of creating unidirectional connectivity between populations of neurons in the two wells. Here we report electrophysiological evidence that supports the hypothesis that the dominant information flow is in the desired direction. This was done by measuring the propagation speed and direction of individual action potentials, with the result that 84% of the spikes propagated in the desired direction. Further, we recorded globally synchronized burst activity on each of the electrodes, identified the timing of the first spike on each electrode, recorded locally synchronized burst activity which is found only in the second well and does not propagate back to the first well, and concluded that this measure of burst propagation supports the hypothesis of a unidirectionally connected network. Two hypotheses are discussed for mechanism underlying the activity pattern of the particular neural networks.

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Section: Introductionmentioning

confidence: 99%

Propagation of action potential activity in a predefined microtunnel neural network

et al. 2011

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“…Explant cultures of E15 dorsal root ganglia (DRG) from Sprague-Dawley rats were prepared for culture in the microsystem as previously described in [11,12]. Media was Eagle's MEM supplemented with 1% N 2 supplement and 7S NGF (Alomone Labs, Jerusalem, Israel) at 100ng/ml.…”

Section: Culture Protocolmentioning

confidence: 99%

Spatiotemporal localization of injury potentials in DRG neurons during vincristine-induced axonal degeneration

Ravula

Wang

McClain

et al. 2007

Neuroscience Letters

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The distal to proximal degeneration of axons, or "dying back" is a common pattern of neuropathology in many diseases of the PNS and CNS. A long-standing debate has centered on whether this pattern of neurodegeneration is due to an insult to the cell body or to the axon itself, although it is likely that mechanisms are different for specific disease entities. We have addressed this question in a model system of vincristine-induced axonal degeneration. Here, we created a novel experimental apparatus combining a microfluidic divider with a multielectrode array substrate to allow for independent monitoring of injury-induced electrical activity from dorsal root ganglion (DRG) cell bodies and axons while isolating them into their own culture microenvironments. At specified doses, exposure of the cell body to vincristine caused neither morphological neurodegeneration nor persistent hyperexcitablility. In comparison, exposure of the distal axon to the same dose of vincristine first caused a decrease in the excitability of the axon and then axonal degeneration in a dying back pattern. Additionally, exposure of axons to vincristine caused an initial period of hyperexcitability in the cell bodies, suggesting that a signal is transmitted from the distal axon to the soma during the progression of vincristine-induced axonal degeneration. These data support the proposition that vincristine has a direct neurotoxic effect on the axon.

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“…These short-term (i.e., <1 wk) cultures have limited capacity to generate robust networks since in vitro cultures take weeks (>21 days) to fully develop mature axon connections (Dichter., 1978, Brewer et al, 1993). For these reasons, microfluidic structures such as microchannels (or tunnels) for the physical isolation of neuronal cells have been intensively investigated to generate long-term cultured neural networks (Claverol-Tinture and Pine., 2002, Bani-Yaghoub et al, 2005, Morin et al, 2005, Ravula et al, 2006, Dworak and Wheeler., 2009). While much progress has been made, the short distance of axons (≤500 μm) in these small neural circuits are not ideal for axon tract accessibility.…”

Section: Introductionmentioning

confidence: 99%

Neural circuits with long-distance axon tracts for determining functional connectivity

Tang-Schomer

Davies

Graziano

et al. 2014

Journal of Neuroscience Methods

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The cortical circuitry in the brain consists of structurally and functionally distinct neuronal assemblies with reciprocal axon connections. To generate cell culture-based systems that emulate axon tract systems of an in vivo neural network, we developed a living neural circuit consisting of compartmentalized neuronal populations connected by arrays of two millimeter-long axon tracts that are integrated on a planar multi-electrode array (MEA). The millimeter-scale node-to-node separation allows for pharmacological and electrophysiological manipulations to simultaneously target multiple neuronal populations. The results show controlled selectivity of dye absorption by neurons in different compartments. MEA-transmitted electrical stimulation of targeted neurons shows ∼46% increase of intracellular calcium levels with 20 Hz stimulation, but ∼22% decrease with 2k Hz stimulation. The unique feature of long distance axons promotes in vivo-like fasciculation. These axon tracts are determined to be inhibitory afferents by showing increased action potential firing of downstream node upon selective application of γ-aminobutyric acid (GABA) to the upstream node. Together, this model demonstrates integrated capabilities for assessing multiple endpoints including axon tract tracing, calcium influx, network architecture and activities. This system can be used as a multi-functional platform for studying axon tract-associated CNS disorders in vitro, such as diffuse axonal injury after brain trauma.

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A multielectrode microcompartment culture platform for studying signal transduction in the nervous system

Cited by 26 publications

References 34 publications

Propagation of action potential activity in a predefined microtunnel neural network

Propagation of action potential activity in a predefined microtunnel neural network

Spatiotemporal localization of injury potentials in DRG neurons during vincristine-induced axonal degeneration

Neural circuits with long-distance axon tracts for determining functional connectivity

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