Inhibition of microRNA 128 promotes excitability of cultured cortical neuronal networks

Genome Res. 2016 Oct;26(10):1411-1416. doi: 10.1101/gr.199828.115. Epub 2016 Aug 11.

Abstract

Cultured neuronal networks monitored with microelectrode arrays (MEAs) have been used widely to evaluate pharmaceutical compounds for potential neurotoxic effects. A newer application of MEAs has been in the development of in vitro models of neurological disease. Here, we directly evaluated the utility of MEAs to recapitulate in vivo phenotypes of mature microRNA-128 (miR-128) deficiency, which causes fatal seizures in mice. We show that inhibition of miR-128 results in significantly increased neuronal activity in cultured neuronal networks derived from primary mouse cortical neurons. These results support the utility of MEAs in developing in vitro models of neuroexcitability disorders, such as epilepsy, and further suggest that MEAs provide an effective tool for the rapid identification of microRNAs that promote seizures when dysregulated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials*
  • Animals
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • Neurons / metabolism
  • Neurons / physiology*
  • Patch-Clamp Techniques / methods*
  • Seizures / genetics*
  • Seizures / physiopathology
  • Tissue Array Analysis / methods*

Substances

  • MicroRNAs
  • Mirn128 microRNA, mouse

Associated data

  • figshare/10.6084/m9.figshare.3543728.v2
  • figshare/10.6084/m9.figshare.3521726.v4
  • figshare/10.6084/m9.figshare.3521621.v3
  • figshare/10.6084/m9.figshare.3521291.v4
  • figshare/10.6084/m9.figshare.3543341.v2
  • figshare/10.6084/m9.figshare.3543467.v1
  • figshare/10.6084/m9.figshare.3524531.v3
  • figshare/10.6084/m9.figshare.3524483.v1
  • figshare/10.6084/m9.figshare.3524447.v1
  • figshare/10.6084/m9.figshare.3524360.v2