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J Neurotrauma. 2015 Jul 1;32(13):1011-9. doi: 10.1089/neu.2014.3667. Epub 2015 Apr 24.

Alterations in Hippocampal Network Activity after In Vitro Traumatic Brain Injury.

Author information

1
1 Department of Biomedical Engineering, Columbia University , New York, New York.
2
2 Department of Electrical Engineering, Princeton University , Princeton, New Jersey.
3
3 Department of Chemistry and Biochemistry, Arizona State University , Tempe, Arizona.
4
4 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.

Abstract

Traumatic brain injury (TBI) alters function and behavior, which can be characterized by changes in electrophysiological function in vitro. A common cognitive deficit after mild-to-moderate TBI is disruption of persistent working memory, of which the in vitro correlate is long-lasting, neuronal network synchronization that can be induced pharmacologically by the gamma-aminobutyric acid A antagonist, bicuculline. We utilized a novel in vitro platform for TBI research, the stretchable microelectrode array (SMEA), to investigate the effects of TBI on bicuculline-induced, long-lasting network synchronization in the hippocampus. Mechanical stimulation significantly disrupted bicuculline-induced, long-lasting network synchronization 24 h after injury, despite the continued ability of the injured neurons to fire, as revealed by a significant increase in the normalized spontaneous event rate in the dentate gyrus (DG) and CA1. A second challenge with bicuculline 24 h after the first challenge significantly decreased the normalized spontaneous event rate in the DG. In addition, we illustrate the utility of the SMEA for TBI research by combining multiple experimental paradigms in one platform, which has the potential to enable novel investigations into the mechanisms responsible for functional consequences of TBI and speed the rate of drug discovery.

KEYWORDS:

electrophysiology; hippocampus; network synchronization; traumatic brain injury

PMID:
25517970
DOI:
10.1089/neu.2014.3667
[Indexed for MEDLINE]
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