Effects of mild traumatic brain injury on hippocampal synaptic plasticity and behaviour in juvenile rats




Pinar Cabeza de Vaca, Cristina

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Traumatic Brain Injury (TBI) is a global health problem and concussion, or mild TBI (mTBI), accounts for up to 75% of all brain injuries occurring annually in the US. There is also growing awareness that repeated mild traumatic brain injury (r-mTBI) can result in cumulative neuropathology and learning and memory deficits, however there is a paucity of preclinical data as to the extent these deficits manifest. R-mTBI in juvenile populations is of special interest as not only is this a high risk group, but this is also a time period when the human brain continues to mature. The hippocampus is a brain region important for learning and memory processes, and r-mTBI during the juvenile period may particularly disrupt the development of cognitive processes. To examine this issue we used a model of awake closed head injury (ACHI), and administered 8 impacts over a 4 day period to juvenile male and female rats (P25-28). At 1 or 7 days after the last injury, a cohort of rats was used for behavioural testing to study anxiety and risk-taking behaviours and cognitive abilities. From a different cohort, hippocampal slices were generated and used for in vitro electrophysiological recordings, and the capacity for long-term depression (LTD) and long-term potentiation (LTP) was examined in the medial perforant path (MPP)-dentate gyrus (DG) synapse. Our results showed that r-mTBI impaired hippocampal-dependent spatial learning and memory and that r-mTBI significantly impaired the capacity for LTD but not LTP in both sexes. These data are the first to describe the negative impact of r-mTBI on LTD in the juvenile DG in both males and females, and provide evidence for the delayed development of neurological deficits with r-mTBI.



neuroscience, concussion, learning and memory, mTBI, hippocampus