Brain-on-a chip technologies for investigating neuronal diseases: Toward precision medicine applications

M. Frega, B. Mossink, K. Linda, J. Keller, D. Schubert, N. Nadif Kasri

Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review

2 Citations (Scopus)


Neurodevelopmental disorders (NDDs) are a collection of heterogeneous syndromes involving disruption of early neurobiological development. While the identification of disease genes has great benefits for diagnostic and prognostic purposes, for the vast majority of these genes there is little knowledge about neurobiological mechanisms that they control at the cellular and network level. Recent studies demonstrate that NDDs are 'diseases of the synapse'. Synaptic malfunction can severely affect network connectivity and dynamic. Understanding the neural circuit basis of NDDs is therefore imperial for a better understanding of these disorders. Kleefstra syndrome (KS) is a NDD characterized by moderate to severe intellectual disability, childhood hypotonia, and facial dysmorphism associated with genes deficiency. Here, we studied how KS genes-deficiency affects neuronal network maturation using dissociated neuronal cultures (i.e. from rodent or KS patient induced pluripotent stem cells). Using micro-electrode arrays technology we characterized the electrophysiological activity of control and KS genes-deficient neuronal networks. We showed that KS genes-deficient neuronal networks exhibited different pattern of synchronous activity compared to control condition. In particular, KS genes-deficiency induced an inappropriate network organization and irregular pattern of activity, indicating that KS genes are required for proper network formation. The neuronal network phenotype found here, provides for relevant future directions in the elucidation of pathophysiology in KS.

Original languageEnglish
Title of host publication2018 IEEE International Symposium on Circuits and Systems, ISCAS 2018 - Proceedings
Place of PublicationPiscataway, NJ
ISBN (Electronic)978-1-5386-4881-0
ISBN (Print)978-1-5386-4882-7
Publication statusPublished - 26 Apr 2018
Externally publishedYes
Event2018 IEEE International Symposium on Circuits and Systems, ISCAS 2018 - Firenze Fiera Congress & Exhibition Center, Florence, Italy
Duration: 27 May 201830 May 2018


Conference2018 IEEE International Symposium on Circuits and Systems, ISCAS 2018
Abbreviated titleISCAS 2018


  • Derived neurons
  • iPSCs
  • Micro-electrode arrays
  • Neurodevelopmental disorders

Cite this