An Overview of Studies Demonstrating that ex vivo Neuronal Networks Display Multiple Complex Behaviors: Emergent Properties of Nearest-Neighbor Interactions of Excitatory and Inhibitory Neurons.

Thomas B. Shea1, *
1 Laboratory for Neuroscience, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA

© 2021 Thomas B. Shea

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Laboratory for Neuroscience, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854 USA; Tel: 978-934-2881: Fax: 978-934-3044 E-mail:


The responsiveness of the human nervous system ranges from the basic sensory interpretation and motor regulation to so-called higher-order functions such as emotion and consciousness. Aspects of higher-order functions are displayed by other mammals and birds. In efforts to understand how neuronal interaction can generate such a diverse functionality, murine embryonic cortical neurons were cultured on Petri dishes containing multi-electrode arrays that allowed recording and stimulation of neuronal activity. Despite the lack of major architectural features that govern nervous system development in situ, this overview of multiple studies demonstrated that these 2-dimensional ex vivo neuronal networks nevertheless recapitulate multiple key aspects of nervous system development and activity in situ, including density-dependent, the spontaneous establishment of a functional network that displayed complex signaling patterns, and responsiveness to environmental stimulation including generation of appropriate motor output and long-term potentiation. These findings underscore that the basic interplay of excitatory and inhibitory neuronal activity underlies all aspects of nervous system functionality. This reductionist system may be useful for further examination of neuronal function under developmental, homeostatic, and neurodegenerative conditions.

Keywords: Neuronal culture, Multi-electrode arrays, Synaptic signaling, Inhibitory neurons, Excitatory neurons, Nervous system development.