Dynamic changes in neural circuit topology following mild mechanical injury in vitro

Tapan P. Patel, Scott C. Ventre, David F. Meaney

Research output: Contribution to journalArticle

Abstract

Despite its enormous incidence, mild traumatic brain injury is not well understood. One aspect that needs more definition is how the mechanical energy during injury affects neural circuit function. Recent developments in cellular imaging probes provide an opportunity to assess the dynamic state of neural networks with single-cell resolution. In this article, we developed imaging methods to assess the state of dissociated cortical networks exposed to mild injury. We estimated the imaging conditions needed to achieve accurate measures of network properties, and applied these methodologies to evaluate if mild mechanical injury to cortical neurons produces graded changes to either spontaneous network activity or altered network topology. We found that modest injury produced a transient increase in calcium activity that dissipated within 1 h after injury. Alternatively, moderate mechanical injury produced immediate disruption in network synchrony, loss in excitatory tone, and increased modular topology. A calcium-activated neutral protease (calpain) was a key intermediary in these changes; blocking calpain activation restored the network nearly completely to its pre-injury state. Together, these findings show a more complex change in neural circuit behavior than previously reported for mild mechanical injury, and highlight at least one important early mechanism responsible for these changes.

Original languageEnglish (US)
Pages (from-to)23-36
Number of pages14
JournalAnnals of biomedical engineering
Volume40
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Keywords

  • Calcium indicator dyes
  • Calpain
  • Cluster
  • Concussions
  • Excitatory tone
  • Neural network
  • Stochastic integrate-and-fire model
  • Synchrony
  • Traumatic brain injury

ASJC Scopus subject areas

  • Biomedical Engineering

Fingerprint Dive into the research topics of 'Dynamic changes in neural circuit topology following mild mechanical injury in vitro'. Together they form a unique fingerprint.

  • Cite this