Functional Connectivity of Neural Network in Dissociated Hippocampal Culture Grown on Microelectrode Array
Dissociated neural cultures are used as convenient experimental models to study basic mechanisms of brain signal processing, memory, learning and synaptic plasticity in neuronal networks. Evaluation of short-term and long-term memory in hippocampal cultures requires simultaneous multisite recording of signals and bioelectrical stimulation.
The aim of the investigation was to reveal the characteristic features of neuronal network plasticity in the model of primary hippocampal cell cultures, to study the stability of spontaneous and stimulus-induced changes in spiking patterns of cultures.
Materials and Methods. Long-term changes in functional connectivity characteristics of spikes propagating in the neural network of hippocampal culturesgrown on microelectrode arrays were evaluated. It was investigated how low-frequency stimulation (0.1–0.5 Hz) lying in the frequency band of spontaneous bursting activity altered functional connections in the network at different time scales.
Results. Low-frequency stimulation of hippocampal culturesgrown on microelectrode arrays was found to induce reconfiguration of the network connectivity. This effect could be preserved during tens of minutes. On the time scale of hours, stimulation-induced connectivity pattern disappeared due to spontaneous changes.
- Chiappalone M., Massobrio P., Martinoia S. Network plasticity in cortical assemblies. Eur J Neurosci 2008; 28(1): 221–237, https://doi.org/10.1111/j.1460-9568.2008.06259.x.
- Bakkum D.J., Chao Z.C., Potter S.M. Long-term activity-dependent plasticity of action potential propagation delay and amplitude in cortical networks. PLoS One 2008; 3(5): e2088, https://doi.org/10.1371/journal.pone.0002088.
- Eytan D., Brenner N., Marom S. Selective adaptation in networks of cortical neurons. J Neurosci 2003; 23(28): 9349–9356.
- Marom S., Shahaf G. Development, learning and memory in large random networks of cortical neurons: lessons beyond anatomy. Q Rev Biophys 2002; 35(01): 63–87, https://doi.org/10.1017/s0033583501003742.
- Pimashkin A., Kastalskiy I., Simonov A., Koryagina E., Mukhina I., Kazantsev V. Spiking signatures of spontaneous activity bursts in hippocampal cultures. Front Comput Neurosci 2011; 5: 46, https://doi.org/10.3389/fncom.2011.00046.
- Shahaf G., Eytan D., Gal A.,
Kermany E., Lyakhov V., Zrenner C., Marom S. Order-based representation in random networks of cortical neurons. PLoS Comput Biol 2008; 4(11): e1000228, https://doi.org/10.1371/journal.pcbi.1000228. - Maccione A., Garofalo M.,
Nieus T., Tedesco M., Berdondini L., Martinoia S. Multiscale functional connectivity estimation on low-density neuronal cultures recorded by high-density CMOS Micro Electrode Arrays. J Neurosci Methods 2012; 207(2): 161–171, https://doi.org/10.1016/j.jneumeth.2012.04.002. - Makarov V.A., Panetsos F., de Feo O. A method for determining neural connectivity and inferring the underlying network dynamics using extracellular spike recordings. J Neurosci Methods 2005; 144(2): 265–279, https://doi.org/10.1016/j.jneumeth.2004.11.013.
- Ullo S.,
Nieus T.R., Sona D., Maccione A., Berdondini L., Murino V. Functional connectivity estimation over large networks at cellular resolution based on electrophysiological recordings and structural prior. Front Neuroanat 2014; 8: 137, https://doi.org/10.3389/fnana.2014.00137. - Wagenaar D.A. Controlling bursting in cortical cultures with closed-loop multi-electrode stimulation. J Neurosci 2005; 25(3): 680–688, https://doi.org/110.1523/jneurosci.4209-04.2005.
- Poli D., Pastore V.P., Massobrio P. Functional connectivity
in in vitro neuronal assemblies. Front Neural Circuits 2015; 9: 57, https://doi.org/10.3389/fncir.2015.00057. - le Feber J., Witteveen T., van Veenendaal T.M., Dijkstra J. Repeated stimulation of cultured networks of rat cortical neurons induces parallel memory traces. Learn. Mem 2015; 22(12): 594–604, https://doi.org/10.1101/lm.039362.115.
- Bologna L.L.,
Nieus T., Tedesco M., Chiappalone M., Benfenati F., Martinoia S. Low-frequency stimulation enhances burst activity in cortical cultures during development. Neuroscience 2010; 165(3): 692–704, https://doi.org/10.1016/j.neuroscience.2009.11.018. - Maeda E., Kuroda Y., Robinson H.P.C., Kawana A. Modification of parallel activity elicited by propagating bursts in developing networks of rat cortical
neurones . Eur J Neurosci 1998; 10(2): 488–496, https://doi.org/10.1046/j.1460-9568.1998.00062.x. - Vajda I., van Pelt J., Wolters P., Chiappalone M., Martinoia S., van Someren E., van Ooyen A. Low-frequency stimulation induces stable transitions in stereotypical activity in cortical networks. Biophys J 2008; 94(12): 5028–5039, https://doi.org/10.1529/biophysj.107.112730.
- Wagenaar D.A., Pine J., Potter S.M. An extremely rich repertoire of bursting patterns during the development of cortical cultures. BMC Neurosci 2006; 7(1): 11, https://doi.org/10.1186/1471-2202-7-11.
- le Feber J., Rutten W.L., Stegenga J., Wolters P.S., Ramakers G.J., van Pelt J. Conditional firing probabilities in cultured neuronal networks: a stable underlying structure in widely varying spontaneous activity patterns. J Neural Eng 2007; 4(2): 54–67, https://doi.org/10.1088/1741-2560/4/2/006.
- Pimashkin A., Gladkov A.,
Agrba E., Mukhina I., Kazantsev V. Selectivity ofstimulus induced responses in cultured hippocampal networks on microelectrode arrays. Cogn Neurodyn 2016; 10(4): 287–299, https://doi.org/10.1007/s11571-016-9380-6.
