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. 2019 Sep 6;13:377. doi: 10.3389/fncel.2019.00377

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Copyright © 2019 Teppola, Aćimović and Linne.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The influence of gradual application of the excitatory receptor antagonists on ISIs, IBIs and network-wide electrode recruitment speed at the beginning of the bursts. (A) The excitatory receptor dependence on ISIs within NBs. Average ISI distribution gradually shifts toward higher fractions in gradually AMPAR blocked networks (n = 2) (top panel), meaning significantly longer distances between spikes within NBs in neurons probed by 1 and 10 μM NBQX (p_ranksum < 0.001). In contrast, the average ISI distribution shifts toward slightly lower fractions in gradually NMDAR blocked networks (n = 2) (bottom panel), meaning significantly shorter distances between spikes within NBs in neurons probed by 10 μM D-AP5 (p_ranksum < 0.001). (B) A change in the excitatory receptor balance modulates the duration of IBIs and thus the frequency of NB events. Neurons in gradually AMPAR blocked networks with 1 and 10 μM NBQX expressed bimodal distributions with significantly shorter and longer IBIs than neurons in CTRL or in 0.1 μM NBQX blocked networks (p_ranksum < 0.001) (top panel). The IBI distributions gradually shifted toward higher fractions in gradually NMDAR blocked networks (bottom panel), meaning significantly longer distances between NBs in neurons probed by 1 and 10 μM D-AP5 in comparison to the CTRL condition (p_ranksum < 0.001). Wilcoxon rank sum test and p-values were computed for all ISIs and IBIs in each condition and in each culture. If the tests showed similar results and p-values for every culture, the results were displayed in (A,B). ^∗∗∗p_ranksum < 0.001, ^∗∗p_ranksum < 0.01, ^∗p_ranksum < 0.05. The x-scale is logarithmic. (C) A change in the excitatory receptor modulates network-wide electrode recruitment speed at the beginning of the NBs (left panel). The network recruitment speed slowed down gradually with gradual AMPAR blockade (0.1, 1, and 10 μM NBQX) (left panel) and sped up gradually with gradual NMDAR blockade (0.1, 1, and 10 μM D-AP5) (right panel). Values were normalized to the CTRL conditions. Bin width is 0.1 ms.

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