Review
Investigating neuronal activity with planar microelectrode arrays: achievements and new perspectives

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Neuronal networks underlie memory storage and information processing in the human brain, and ultimately participate in what Eccles referred to as “the creation of consciousness”. Moreover, as physiological dysfunctions of neurons almost always translate into serious health issues, the study of the dynamics of neuronal networks has become a major avenue of research, as well as their response to pharmacological tampering. Planar microelectrode arrays represent a unique tool to investigate such dynamics and interferences, as they allow one to observe the activity of neuronal networks spread in both space and time. We will here review the major results obtained with microelectrode arrays and give an overview of the latest technological developments in the field, including our own efforts to develop the potential of this already powerful technology.

Section snippets

Overview of pMEA technology

The substrate of choice for pMEAs is glass, though alternative solutions, such as silicon (23, 24), have been proposed. Generally, microelectrodes are made of gold and often covered with platinum black to lower their impedance. Other materials that present a high nanoporosity are also used for microelectrodes, such as titanium nitride (example: pMEAs from Multichannel Systems), for a high electrode capacitance is desirable insofar as faradaic processes may harm the neurons. Interconnects are

The bursting phenomenon: description and analysis

A very general observation about neuronal networks cultured over microelectrode arrays is that, regardless of their origin, they all develop some sort of synchronous bursting activity when they mature (42, 43): depending on the cell culture system used, a consistent bursting activity is likely to dominate after 18 to 25 d in vitro, though there are many departures from this norm (42). During episodes of synchronized bursting, most neurons experience a rapid, transient (a few hundred

Pharmacological tampering with network activity: salient results

Dispersed cultures of neuronal cells in vitro have been shown to be very sensitive to the presence of neuroactive compounds in the culture medium (71, 72), which translates into changes in the recorded patterns of spike activity. Moreover, neuronal networks were found to respond in a histiotypic fashion (dependant on the tissue of origin) to substances tampering with cell receptors (59, 73). Quite naturally, neuronal networks grown on pMEAs received a lot of attention as biosensors (23, 72, 74,

Network response to electrical stimulation: adaptation and learning

The usefulness of pMEAs comes not only from their capacity to record from cells cultured on top of them, but also from their ability to stimulate these cells. Extracellular stimulation, however, is not as simple as it may sound (90). Indeed, recording is usually impossible for the duration of the stimulation, since the amplitude of the stimulus itself is usually at least one order of magnitude bigger than the neuronal signals; moreover, it creates strong artifacts on most channels that prevent

Developments centered on pMEAs

A few attempts have been made to deviate from the traditional design of pMEAs and propose innovative concepts to improve the interface between microelectrodes and cells in culture. Regehr and co-workers presented a system where an electrode was placed on a rigid silicon micro-board and manually pressed on top of a cell (97). Though a high signal-to-noise ratio could be obtained, the cumbersome nature of the whole set-up meant this concept was not developed further by its inventors. A

Conclusion

Planar microelectrode array technology provides a unique insight into the dynamics of neuronal networks in culture. Thus, they can be integrated into multiple lines of research, as depicted in Fig. 8. In particular, the development of complete experimental platforms enabling continuous, long-term monitoring of these networks has recently yielded a wealth of information regarding the spatiotemporal patterns of activity that arise and change as cultures maturate. This is undoubtedly a great

Acknowledgements

F.M. wishes to thank Dr. Mun’delanji Vestergaard for critical reading of the manuscript.

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