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Published February 7, 2006 | Published
Journal Article Open

An extremely rich repertoire of bursting patterns during the development of cortical cultures


Background: We have collected a comprehensive set of multi-unit data on dissociated cortical cultures. Previous studies of the development of the electrical activity of dissociated cultures of cortical neurons each focused on limited aspects of its dynamics, and were often based on small numbers of observed cultures. We followed 58 cultures of different densities---3000 to 50,000 neurons on areas of 30 to 75 mm^2---growing on multi-electrode arrays (MEAs) during the first five weeks of their development. Results: Plating density had a profound effect on development. While the aggregate spike detection rate scaled linearly with density, as expected from the number of cells in proximity to electrodes, dense cultures started to exhibit bursting behavior earlier in development than sparser cultures. Analysis of responses to electrical stimulation suggests that axonal outgrowth likewise occurred faster in dense cultures. After two weeks, the network activity was dominated by population bursts in most cultures. In contrast to previous reports, development continued with changing burst patterns throughout the observation period. Burst patterns were extremely varied, with inter-burst intervals between 1 and 300 s, different amounts of temporal clustering of bursts, and different firing rate profiles during bursts. During certain stages of development bursts were organized into tight clusters with highly conserved internal structure. Conclusions: Dissociated cultures of cortical cells exhibited a much richer repertoire of activity patterns than previously reported. Except for the very sparsest cultures, all cultures exhibited globally synchronized bursts, but bursting patterns changed over the course of development, and varied considerably between preparations. This emphasizes the importance of using multiple preparations---not just multiple cultures from one preparation---in any study involving neuronal cultures. These results are based on 963 half-hour-long recordings. To encourage further investigation of the rich range of behaviors exhibited by cortical cells in vitro, we are making the data available to other researchers, together with Matlab code to facilitate access.

Additional Information

© 2006 Wagenaar et al., licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Submission date 1 Sep 2005; Acceptance date 7 Feb 2006; Publication date 7 Feb 2006 Authors' contributions: DAW collected all data, performed the analysis, and prepared text and figures for the manuscript. JP contributed to the design of the study and to the preparation of the manuscript. SMP was instrumental to the conception of this study, helped interpret the results, and contributed to the preparation of the manuscript. Acknowledgments: We thank our lab technician, Sheri McKinney. This work was partially supported by NINDS grants NS38628 (to SMP) and NS44134 (to JP), by NIBIB grant EB00786 (to SMP), by the NSF Center for Behavioral Neuroscience, and by the Whitaker Foundation. All raw data used for this report may be obtained from the web, at http://potterlab.bme.gatech.edu/development-data. Analogues of Figure 1 for each of the 58 cultures studied are available at the same location. Requests for access may be sent to Steve Potter (steve.potter@bme.gatech.edu)

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