Synaptic signal streams generated by ex vivo neuronal networks contain non‐random, complex patterns

Abstract

Cultured embryonic neurons develop functional networks that transmit synaptic signals over multiple sequentially connected neurons as revealed by multi-electrode arrays (MEAs) embedded within the culture dish. Signal streams of ex vivo networks contain spikes and bursts of varying amplitude and duration. Despite the random interactions inherent in dissociated cultures, neurons are capable of establishing functional ex vivo networks that transmit signals among synaptically connected neurons, undergo developmental maturation, and respond to exogenous stimulation by alterations in signal patterns. These characteristics indicate that a considerable degree of organization is an inherent property of neurons. We demonstrate herein that (1) certain signal types occur more frequently than others, (2) the predominant signal types change during and following maturation, (3) signal predominance is dependent upon inhibitory activity, and (4) certain signals preferentially follow others in a non-reciprocal manner. These findings indicate that the elaboration of complex signal streams comprised of a non-random distribution of signal patterns is an emergent property of ex vivo neuronal networks.

Spontaneous Neuronal Signaling is Inherently Musical and Mathematical: Insight into the Universal Human Affinity for Music

“…Despite the random synaptogenesis inherent in dissociated cultures, ex vivo neuronal networks neurons retain the ability to transmit information in an organized manner [13]. Notably, synaptic signals are comprised of multiple all -or -none signals and therefore are inherently digital.…”

Pathway Analysis: State of the Art

“…Following advancements in pathway annotation from PDBs, topology of the underlying networks of pathways has been made publicly available through different databases, following immediate integration into PA methodologies. This was greatly encouraged by the increased attention network theory had in life sciences (Amaral and Ottino, 2004 ; Emmert-Streib and Dehmer, 2011 ).…”

“…Limitations to PTB methodologies are hard to address as they portray a change in one of the current paradigms in life sciences. Life components do not work isolated, functioning by their own, they rather do so in precise concert to accomplish life functions, and their behavior as a whole system is dynamic, adaptable and robust (Hartwell et al, 1999 ; Tononi et al, 1999 ; Amaral and Ottino, 2004 ). In summary, life is a complex system.…”

“…Our current theoretical framework in Omic research has developed around the assumption that analysis of HTBD information should help to understand the underlying mechanisms that determine biological phenotypes. This assumption has proven effective in many instances, but interpretation of HTBD is not straightforward, as we unveil how truly complex life is (Amaral and Ottino, 2004 ).…”

“…In contrast, living organisms “machinery” has proven to be even more complex to understand, having large number of components that may act by following dynamic rules that are not well-understood. Thus, the study of isolated biological components is not enough to understand biological systems, leaving many questions still open, for instance, the ones related with the functioning of the human brain and the development of multifactorial diseases (Amaral and Ottino, 2004 ).…”