Long-term potentiation and long-term depression are both impaired afterin vitrostretch injury measured with stretchable microelectrode arrays.

Abstract

Objective. Traumatic brain injury (TBI) is a prevalent injury that can lead to long term deficits in memory and cognition. Predicting which patients will have long lasting memory issues following mild TBI is challenging.Approach.Organotypic hippocampal slice cultures were biaxially stretched to model a TBI. In thisin vitromodel, stretchable microelectrode arrays were embedded within the culture substrate to both deform the adhered culture and record neural signals, which are indicators of neuronal health and network connectivity. Multiple spontaneous and evoked recordings were obtained while maintaining sterility to study and modulate the electrophysiological response to injury.Main results. In the first set of experiments, neural signals were measured 2 and 24 h after stretch injury. Bursting activity increased 2 h after injury but returned to baseline by 24 h. However, 24 h after injury, both long-term potentiation (LTP) and long-term depression (LTD) were impaired. In another experiment, LTP was induced multiple times, both 24 h before and 24 h after injury, to study how the state of the pre-injury network affected electrophysiological outcome after injury. We provide preliminary evidence that induction of LTP before injury to increase synaptic strength was detrimental to neuronal plasticity (LTP) after injury. Future studies can use the stretchable microelectrode arrays and our induction paradigm to test if induction of LTD, a weakening of synaptic strength, could increase resiliency to injury.Significance.This research begins to examine the role of pre-injury network connectivity and synaptic strength on post-traumatic electrophysiological outcomes, which may increase understanding of the determinants of heterogeneous clinical outcomes in mild TBI.