Gupta Akshay, Dovek Laura, Proddutur Archana, Elgammal Fatima S, Santhakumar Vijayalakshmi
Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ, United States.
Department of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, CA, United States.
Front Neurosci. 2022 Mar 14;16:800733. doi: 10.3389/fnins.2022.800733. eCollection 2022.
Progressive physiological changes in the hippocampal dentate gyrus circuits following traumatic brain injury (TBI) contribute to temporal evolution of neurological sequelae. Although early posttraumatic changes in dentate synaptic and extrasynaptic GABA currents have been reported, and whether they evolve over time and remain distinct between the two projection neuron classes, granule cells and semilunar granule cells, have not been evaluated. We examined long-term changes in tonic GABA currents and spontaneous inhibitory postsynaptic currents (sIPSCs) and in dentate projection neurons 3 months after moderate concussive fluid percussion injury (FPI) in adolescent rats. Granule cell tonic GABA current amplitude remained elevated up to 1 month after FPI, but decreased to levels comparable with age-matched controls by 3 months postinjury. Granule cell sIPSC frequency, which we previously reported to be increased 1 week after FPI, remained higher than in age-matched controls at 1 month and was significantly reduced 3 months after FPI. In semilunar granule cells, tonic GABA current amplitude and sIPSC frequency were not different from controls 3 months after FPI, which contrast with decreases observed 1 week after injury. The switch in granule cell inhibitory inputs from early increase to subsequent decrease could contribute to the delayed emergence of cognitive deficits and seizure susceptibility after brain injury.
创伤性脑损伤(TBI)后海马齿状回回路的渐进性生理变化导致神经后遗症的时间演变。尽管已有报道称创伤后早期齿状突触和突触外GABA电流发生了变化,但它们是否随时间演变以及在颗粒细胞和半月形颗粒细胞这两种投射神经元类型之间是否保持不同,尚未得到评估。我们研究了青春期大鼠中度冲击性液体冲击伤(FPI)后3个月时齿状投射神经元的持续性GABA电流和自发性抑制性突触后电流(sIPSCs)的长期变化。FPI后长达1个月,颗粒细胞的持续性GABA电流幅度持续升高,但在损伤后3个月降至与年龄匹配对照组相当的水平。我们之前报道FPI后1周颗粒细胞sIPSC频率增加,在1个月时仍高于年龄匹配对照组,而在FPI后3个月显著降低。在半月形颗粒细胞中,FPI后3个月持续性GABA电流幅度和sIPSC频率与对照组无差异,这与损伤后1周观察到的降低形成对比。颗粒细胞抑制性输入从早期增加到随后减少的转变可能导致脑损伤后认知缺陷和癫痫易感性的延迟出现。