title: Interfacing 3D Engineered Neuronal Cultures to Micro-Electrode Arrays: An Innovative In Vitro Experimental Model.
abstract: Currently, large-scale networks derived from dissociated neurons growing and developing in vitro on extracellular micro-transducer devices are the gold-standard experimental model to study basic neurophysiological mechanisms involved in the formation and maintenance of neuronal cell assemblies. However, in vitro studies have been limited to the recording of the electrophysiological activity generated by bi-dimensional (2D) neural networks. Nonetheless, given the intricate relationship between structure and dynamics, a significant improvement is necessary to investigate the formation and the developing dynamics of three-dimensional (3D) networks. In this work, a novel experimental platform in which 3D hippocampal or cortical networks are coupled to planar Micro-Electrode Arrays (MEAs) is presented. 3D networks are realized by seeding neurons in a scaffold constituted of glass microbeads (30-40 µm in diameter) on which neurons are able to grow and form complex interconnected 3D assemblies. In this way, it is possible to design engineered 3D networks made up of 5-8 layers with an expected final cell density. The increasing complexity in the morphological organization of the 3D assembly induces an enhancement of the electrophysiological patterns displayed by this type of networks. Compared with the standard 2D networks, where highly stereotyped bursting activity emerges, the 3D structure alters the bursting activity in terms of duration and frequency, as well as it allows observation of more random spiking activity. In this sense, the developed 3D model more closely resembles in vivo neural networks.
authors.affiliation: Department of Informatics, Bioengineering, Robotics and System Engineering (DIBRIS), University of Genova.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Tedesco
authors.affiliation: Department of Informatics, Bioengineering, Robotics and System Engineering (DIBRIS), University of Genova; Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Center.
authors.forename: Monica
authors.initials: M
authors.lastname: Frega
authors.affiliation: Department of Informatics, Bioengineering, Robotics and System Engineering (DIBRIS), University of Genova.
authors.forename: Sergio
authors.initials: S
authors.lastname: Martinoia
authors.affiliation: Fondazione Istituto Italiano di Tecnologia (IIT).
authors.forename: Mattia
authors.initials: M
authors.lastname: Pesce
authors.affiliation: Department of Informatics, Bioengineering, Robotics and System Engineering (DIBRIS), University of Genova; paolo.massobrio@unige.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Massobrio
mesh_terms: D000818:Animals; D005260:Female; D005898:Glass / Q000737:chemistry; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D008839:Microelectrodes; D008863:Microspheres; D008962:Models, Theoretical; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D023822:Tissue Engineering; D054457:Tissue Scaffolds