title: Axon diodes for the reconstruction of oriented neuronal networks in microfluidic chambers.
abstract: Various experimental models are used to study brain development and degeneration. They range from whole animal models, which preserve anatomical structures but strongly limit investigations at the cellular level, to dissociated cell culture systems that allow detailed observation of cell phenotypes but lack the highly ordered physiological neuron connection architecture. We describe here a platform comprising independent cell culture chambers separated by an array of "axonal diodes". This array involves asymmetric micro-channels, imposing unidirectional axon connectivity with 97% selectivity. It allows the construction of complex, oriented neuronal networks not feasible with earlier platforms. Different neuronal subtypes could be co-cultivated for weeks, and sequential seeding of different cell populations reproduced physiological network development. To illustrate possible applications, we created and characterized a cortico-striatal oriented network. Functional synaptic connections were established. The activation of striatal differentiation by cortical axons, and the synchronization of neural activity were demonstrated. Each neuronal population and subcompartment could be chemically addressed individually. The directionality of neural pathways being a key feature of the nervous system organization, the axon diode concept brings in a paradigmatic change in neuronal culture platforms, with potential applications for studying neuronal development, synaptic transmission and neurodegenerative disorder such as Alzheimer and Parkinson diseases at the sub-cellular, cellular and network levels.
authors.affiliation: Laboratoire de Neurobiologie des Processus Adaptatifs, CNRS, UMR7102, Université Pierre et Marie Curie, Paris, France. jean-michel.peyrin@snv.jussieu.fr
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Peyrin
authors.forename: Bérangère
authors.initials: B
authors.lastname: Deleglise
authors.forename: Laure
authors.initials: L
authors.lastname: Saias
authors.forename: Maéva
authors.initials: M
authors.lastname: Vignes
authors.forename: Paul
authors.initials: P
authors.lastname: Gougis
authors.forename: Sebastien
authors.initials: S
authors.lastname: Magnifico
authors.forename: Sandrine
authors.initials: S
authors.lastname: Betuing
authors.forename: Mathéa
authors.initials: M
authors.lastname: Pietri
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Caboche
authors.forename: Peter
authors.initials: P
authors.lastname: Vanhoutte
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Viovy
authors.forename: Bernard
authors.initials: B
authors.lastname: Brugg
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D001369:Axons / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D046210:Microfluidic Analytical Techniques; D009415:Nerve Net / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D014966:Xanthenes / Q000737:chemistry
chemical_list: D000814:Aniline Compounds; C409648:Fluo 4; D014966:Xanthenes; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium