In vitro cortical neuronal networks as a new high-sensitive system for biosensing applications

• Published in: Biosensors & bioelectronics 2005-04, Vol.20 (10), p.2071-2078
• Main Authors: Martinoia, S., Bonzano, L., Chiappalone, M., Tedesco, M., Marcoli, M., Maura, G.
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Biological and medical sciences; Biological Assay - instrumentation; Biological Assay - methods; Biosensing Techniques - instrumentation; Biosensing Techniques - methods; Biosensors; Biotechnology; Cell Culture Techniques - instrumentation; Cell Culture Techniques - methods; Cell-based biosensor; Cerebral Cortex - drug effects; Cerebral Cortex - embryology; Cerebral Cortex - physiology; Dose-Response Relationship, Drug; Electrophysiological monitoring; Excitatory Amino Acid Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; In vitro cortical neurons; Methods. Procedures. Technologies; Microelectrode arrays; Nerve Net - drug effects; Nerve Net - physiology; Neurons - drug effects; Neurons - physiology; Neuropharmacological investigations; Rats; Reproducibility of Results; Sensitivity and Specificity; Various methods and equipments
• ISSN: 0956-5663; 1873-4235
• DOI: 10.1016/j.bios.2004.09.012

By taking advantages of the main features of the microelectrode array (MEA) technology (i.e. multisite recordings, stable and long-term coupling with the biological preparation), we analyzed the changes in activity patterns induced by applying specific substances to dissociated cortical neurons from rat-embryos (E18). Data were recorded simultaneously from 60 electrodes, and the electrophysiological behavior was investigated during the third week in vitro, both at the spike and burst level. The analysis of the electrophysiological activity modulation, by applying agonists of the ionotropic glutamate receptors at low (i.e. 0.2–1–5 μM) and high (i.e. 50–100 μM) concentrations, is presented. Preliminary results show that the dynamics of the in vitro cortical neurons is very sensitive to pharmacological manipulation of the glutamatergic transmission and the effects on the network behavior are strictly dependent from the drug concentration. In particular, the addition of a high-dose of agonist determined a global and irreversible depression of the network activity, while, in the low-concentration case, the electrophysiological behavior showed different results, depending on the type of receptor involved. From these observations, we are encouraged to think of a more engineered system, based on in vitro cortical neurons, as a novel sensitive system for drug (pre)-screening and neuropharmacological evaluations.