Cerebral cortex
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Persistent motor/cognitive alterations and increased prevalence of Alzheimer's disease are known consequences of recurrent sports concussions, the most prevalent cause of mild traumatic brain injury (TBI) among youth. Animal models of TBI demonstrated that impaired learning was related to persistent synaptic plasticity suppression in the form of long-term potentiation (LTP) and depression (LTD). In humans, single and repeated concussive injuries lead to lifelong and cumulative enhancements of gamma-aminobutyric acid (GABA)-mediated inhibition, which is known to suppress LTP/LTD plasticity. ⋯ Our results indicate that repeated concussions induced persistent elevations of GABA(B)-mediated intracortical inhibition in M1, which was associated with suppressed PAS-induced LTP/LTD-like synaptic plasticity. This synaptic plasticity suppression was related to reduced implicit motor learning on the SRTT task relative to normal LTP/LTD-like synaptic plasticity in unconcussed teammates. These findings identify GABA neurotransmission alterations after repeated concussions and suggest that impaired learning after multiple concussions could at least partly be related to compromised GABA-dependent LTP/LTD synaptic plasticity.
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It is a matter of ongoing debate whether newly generated granule cells contribute to epileptic activity in the hippocampus. To address this question, we investigated neurogenesis and epileptiform activity (EA) along the hippocampal septotemporal axis in the intrahippocampal kainate (KA) mouse model for temporal lobe epilepsy. Multisite intrahippocampal in vivo recordings and immunolabeling for c-Fos showed that the KA-induced status epilepticus (SE) extended along the septotemporal axis of both hippocampi with stronger intensity at ipsilateral temporal and contralateral sites. ⋯ The newborn neurons were hyperexcitable and functionally integrated into the hippocampal network as revealed by patch-clamp recordings. Analysis of chronic EA also showed a differential intensity pattern along the hippocampal axis: EA was low in the septal portion with prominent sclerosis and granule cell dispersion but most pronounced in the transition zone where neurogenesis reappeared. In conclusion, SE stimulates neurogenesis in a position-dependent manner and coincidence of neurogenesis and stronger EA distal to the injection site suggests a proepileptogenic effect of increased neurogenesis.