Precisely Timed Spatiotemporal Patterns of Neural Activity in Dissociated Cortical Cultures

J. D. Rolston, D. A. Wagenaar, and S. M. Potter

36th Annual Meeting of the Society for Neuroscience, Atlanta, GA, 2006. Prog. no. 432.11

Evidence for recurring precisely-timed spatiotemporal patterns of neural activity has been found both in vivo in behaving animals, and in brain slices. We asked whether such patterns also occur in dissociated cortical networks, which lack most of the intrinsic cortical circuitry present in intact brains. Dissociated cultures were prepared from rat neocortex and plated on multielectrode arrays (MEAs) at high density (1,000 cells/mm2). At 35 days in vitro, one minute of spontaneous multiunit activity was recorded from the MEA’s 59 electrodes (n = 10 cultures from 3 separate platings). A template matching algorithm tracked electrode firing times to locate recurrences of precisely-timed activity patterns. Using a template size of 200 ms and a precision of 10 ms, an average of 1365 ± 281 sequences were found per culture, each repeating 2.5 ± 2.4 times/min (range 2 - 99). On average, the patterns involved 5.5 ± 2.1 electrodes and lasted 127.8 ± 7.6 ms. To evaluate significance, these results were compared to shuffled versions of the same datasets. Two shuffling methods were used: spike shuffling, where action potentials are randomly assigned to new electrodes, and spike swapping, where action potentials are randomly swapped between two electrodes. Since longer sequences are less likely to occur by chance than shorter sequences, we compared to shuffled data the number of recurring sequences where each sequence was weighted by its number of recurrences. Significant results for both shuffling conditions were obtained by this metric (P = 0.002 for spike shuffling and P = 0.025 for spike swapping). The above experiments were repeated at two additional precisions, 1 ms and 0.1 ms, both yielding nonsignificant results when compared to shuffled data. Overall, these results indicate that spontaneously active dissociated cortical networks display recurring spatiotemporal patterns of neural activity with each action potential holding a precision of 10 ms. The discovery of such patterns in dissociated cortical networks suggests that these patterns do not rely on the intact brain’s intrinsic circuitry, but are rather a general property of self-organizing biological neural networks.

Potter lab website: http://www.neuro.gatech.edu/groups/potter

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