Traumatic brain injury enhances the intrinsic excitation and excitatory transmission of granule cells

Abstract

AbstractTraumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide, affecting millions of people each year. TBI can lead to a wide range of physical and cognitive impairments. It is also known to impact on neuronal excitability and synaptic functions. Although hippocampal impairments have been widely described following TBI, the specific effects on dentate gyrus (DG), which act as “gatekeeper” of hippocampal information processing and as a filter of excessive or aberrant input activity, remains to be fully elucidated. In this study we investigated the effects of controlled cortical impact (CCI), as a model of TBI, on the excitability of granule cells and excitatory postsynaptic transmission in the DG at three different time periods, 3 days, 15 day and 4 months after the injury. Our results indicate TBI does not provoke changes in passive membrane properties of granule cells. By applying dimensionality reduction analysis of action potential properties, we were able to identify the variables that exhibited significant short-medium and long-term changes. Indeed, we observed that half-width, amplitude and overshoot of action potential were greater in TBI cells at different time points. Conversely, duration of afterhyperpolarization was reduced compared to control cells. Lastly, although amplitude of sEPSC did not show differences among groups at any time point, significant changes in frequency of sEPCS were observed in TBI cells at different time points, which did not follow the same temporal evolution as control animals. These findings indicate that at the long term TBI increases the intrinsic excitation of granule cells and excitatory synaptic activity of the DG.