Abstract
A typical property of isolated cultured neuronal networks of dissociated rat cortical cells is synchronized spiking, called bursting, starting about one week after plating, when the dissociated cells have sufficiently sent out their neurites and formed enough synaptic connections. This paper is the third in a series of three on simulation models of cultured networks. Our two previous studies [26], [27] have shown that random recurrent network activity models generate intra- and inter-bursting patterns similar to experimental data. The networks were noise or pacemaker-driven and had Izhikevich-neuronal elements with only short-term plastic (STP) synapses (so, no long-term potentiation, LTP, or depression, LTD, was included). However, elevated pre-phases (burst leaders) and after-phases of burst main shapes, that usually arise during the development of the network, were not yet simulated in sufficient detail. This lack of detail may be due to the fact that the random models completely missed network topology .and a growth model. Therefore, the present paper adds, for the first time, a growth model to the activity model, to give the network a time dependent topology and to explain burst shapes in more detail. Again, without LTP or LTD mechanisms. The integrated growth-activity model yielded realistic bursting patterns. The automatic adjustment of various mutually interdependent network parameters is one of the major advantages of our current approach. Spatio-temporal bursting activity was validated against experiment. Depending on network size, wave reverberation mechanisms were seen along the network boundaries, which may explain the generation of phases of elevated firing before and after the main phase of the burst shape.In summary, the results show that adding topology and growth explain burst shapes in great detail and suggest that young networks still lack/do not need LTP or LTD mechanisms.
Highlights
Studies on developmental changes in biological neuronal networks may advance our understanding of brain development, activity patterns associated to different stages, or the relationship between connectivity and activity
Elevated pre-phases and after-phases of burst main shapes were not yet explained in sufficient detail. This lack of detail may be due to the fact that the random models completely missed network topology and lacked a growth model, which is essential to study how activity develops with time
We focused on the effect of network topology and its development on the resulting activity patterns
Summary
Studies on developmental changes in biological neuronal networks may advance our understanding of brain development, activity patterns associated to different stages, or the relationship between connectivity and activity. Long-term cultured networks of dissociated rat cortical neurons provide a useful experimental platform for this study [1,2,3,4,5,6,7]. On a relatively long time scale, from several weeks to months in vitro, neuronal cultures undergo major morphological changes in neurite outgrowth and connectivity/topology, with a corresponding impact on activity. Elevated pre-phases (burst leaders) and after-phases of burst main shapes were not yet explained in sufficient detail. This lack of detail may be due to the fact that the random models completely missed network topology and lacked a growth model, which is essential to study how activity develops with time. The present study adds topology and growth and thereby combines neurite growth models and electrical activity models to predict synchronous bursting behavior, their spatial spread (burst waves) as well as their longitudinal development
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