Smith Colin J, Xiong Guoxiang, Elkind Jaclynn A, Putnam Brendan, Cohen Akiva S
Research Institute of Children's Hospital of Philadelphia , Philadelphia, PA , USA ; Neuroscience Graduate Group, University of Pennsylvania School of Medicine , Philadelphia, PA , USA.
Research Institute of Children's Hospital of Philadelphia , Philadelphia, PA , USA.
Front Neurol. 2015 Nov 13;6:240. doi: 10.3389/fneur.2015.00240. eCollection 2015.
More than 2.5 million Americans suffer a traumatic brain injury (TBI) each year. Even mild to moderate TBI causes long-lasting neurological effects. Despite its prevalence, no therapy currently exists to treat the underlying cause of cognitive impairment suffered by TBI patients. Following lateral fluid percussion injury (LFPI), the most widely used experimental model of TBI, we investigated alterations in working memory and excitatory/inhibitory synaptic balance in the prefrontal cortex. LFPI impaired working memory as assessed with a T-maze behavioral task. Field excitatory postsynaptic potentials recorded in the prefrontal cortex were reduced in slices derived from brain-injured mice. Spontaneous and miniature excitatory postsynaptic currents onto layer 2/3 neurons were more frequent in slices derived from LFPI mice, while inhibitory currents onto layer 2/3 neurons were smaller after LFPI. Additionally, an increase in action potential threshold and concomitant decrease in firing rate was observed in layer 2/3 neurons in slices from injured animals. Conversely, no differences in excitatory or inhibitory synaptic transmission onto layer 5 neurons were observed; however, layer 5 neurons demonstrated a decrease in input resistance and action potential duration after LFPI. These results demonstrate synaptic and intrinsic alterations in prefrontal circuitry that may underlie working memory impairment caused by TBI.
每年有超过250万美国人遭受创伤性脑损伤（TBI）。即使是轻度至中度的TBI也会导致长期的神经学影响。尽管其发病率很高，但目前尚无治疗TBI患者认知障碍根本原因的疗法。在最广泛使用的TBI实验模型——侧方流体冲击伤（LFPI）后，我们研究了前额叶皮质工作记忆和兴奋性/抑制性突触平衡的变化。通过T迷宫行为任务评估，LFPI损害了工作记忆。在脑损伤小鼠的脑片上，前额叶皮质记录的场兴奋性突触后电位降低。在LFPI小鼠的脑片上，作用于第2/3层神经元的自发和微小兴奋性突触后电流更频繁，而LFPI后作用于第2/3层神经元的抑制性电流更小。此外，在受伤动物脑片的第2/3层神经元中观察到动作电位阈值增加，同时放电率降低。相反，在作用于第5层神经元的兴奋性或抑制性突触传递中未观察到差异；然而，LFPI后第5层神经元的输入电阻和动作电位时程降低。这些结果表明前额叶神经回路中的突触和内在变化可能是TBI导致工作记忆损害的基础。
