Biphasic changes in hippocampal granule cells after traumatic brain injury.

Abstract

Traumatic brain injury (TBI) leads to a wide range of long-lasting physical and cognitive impairments. Changes in neuronal excitability and synaptic functions in the hippocampus have been proposed to underlie cognitive alterations. The dentate gyrus (DG) acts as a "gatekeeper" of hippocampal information processing and as a filter of excessive or aberrant input activity. In this study, we investigated the effects of controlled cortical impact, a model of TBI, on the excitability of granule cells (GCs) and spontaneous excitatory postsynaptic currents (sEPSCs) in the DG at three time points, 3 days, 15 days and 4 months after the injury in male and female mice. Our results indicate that changes in the short term are related to intrinsic properties, while changes in the long term are more related to input and synaptic activity, in agreement with the notion that TBI-related pathology courses with an acute phase and a later long-term secondary phase. A biphasic response, a reduction in the shorter term and an increase in the long term, was found in TBI neurons in the frequency of sEPSCs. These changes correlated with a loss of complexity in the pattern of the synaptic input, an alteration that could therefore play a role in the chronic and recurrent TBI-associated hyperexcitation.