Alterations in Hippocampal Network Activity afterIn VitroTraumatic Brain Injury

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.

A multilayer network model of neuron-astrocyte populations in vitro reveals mGluR5inhibition is protective following traumatic injury

“…Previous studies using other in vitro models have shown that mechanical injury to neurons reduces functional connectivity ( 13–15 ). In line with these studies, our results show that single-cell tap injury to multiple neurons reduces overall network connectivity, likely because injury leads to functional uncoupling of a neuron and its neighbors.…”

“…Based on the large body of evidence supporting a role for astrocytes in establishing neural population synchronization and in protecting against neural degeneration following traumatic brain injury (TBI) ( 12, 13 ), we hypothesized that astrocytes aid in the recovery of neuronal network synchrony, which is disrupted following moderate mechanical injury to neural tissue ( 14, 15 ). To test this hypothesis, we subjected neurons in mixed cultures to targeted injury after mGluR 5 inhibition.…”

Phosphodiesterase-4 inhibition restored hippocampal long term potentiation after primary blast

“…In brief, neural event activity was detected based on the multi-resolution Teager energy operator (Choi et al, 2006; Kang et al, 2014; Kang and Morrison, 2014, 2015; Patel et al, 2015). Data from each electrode was segregated by anatomical ROI (dentate gyrus [DG], cornu ammonis 1 [CA1], cornu ammonis 3 [CA3]).…”

“…Spontaneous network synchronization was also quantified using previously published methods (Kang et al, 2014; Li et al, 2007; Li et al, 2010; Patel et al, 2012; Vogel et al, 2016a). In brief, correlation between neural events was calculated for each electrode pair based upon neural event-timing, where two events occurring within 1.5 ms were considered synchronous, and the total number of events.…”

Uniaxial strain of cultured mouse and rat cardiomyocyte strands slows conduction more when its axis is parallel to impulse propagation than when it is perpendicular

“…To address our hypothesis, we took advantage of a recently developed technology to fabricate stretchable silicone‐based microelectrode arrays (sMEAs). The arrays consist of thermally evaporated thin gold electrodes and leads, patterned and embedded in polydimethylsiloxane (PDMS) membranes, as illustrated in Figure . The intrinsic microstructure of the gold film on PDMS (Figure B) enables reversible deformation of the metallic film to tens of per cent of applied strain .…”