Repetitive mild traumatic brain injury induces persistent alterations in spontaneous synaptic activity of hippocampal CA1 pyramidal neurons.
Repetitive mild traumatic brain injury induces persistent alterations in spontaneous synaptic activity of hippocampal CA1 pyramidal neurons.
复制标题
DOI：
10.1016/j.ibneur.2022.02.002
复制
发表时间：
2022-06
影响因子：
1.5
通讯作者：
Nugent, Fereshteh S.
中科院分区：
文献类型：
--
作者：
Langlois, Ludovic D.;Selvaraj, Prabhuanand;Simmons, Sarah C.;Gouty, Shawn;Zhang, Yumin;Nugent, Fereshteh S.
轻度创伤性脑损伤（mTBI）或脑震荡是最常见的创伤性脑损伤形式，通常会导致受影响个体持续的认知障碍和记忆缺陷。尽管大多数研究已经研究了单次损伤后早期海马突触功能障碍的作用，但mTBI对多发性脑脑震荡后海马突触传递的长期影响尚未得到很好的阐明。使用重复性闭合性脑损伤（3XCHI）小鼠mTBI模型，我们通过记录损伤后2周成年雄性小鼠自发性兴奋性AMPA受体（AMPAR）和抑制性gabaar介导的突触后电流（分别为sEPSCs和sIPSCs）来检测海马CA1锥体神经元自发突触传递的改变。我们发现mTBI增强了CA1锥体神经元的突触后兴奋性AMPAR突触功能，而抑制了突触后抑制性GABAAR突触功能。此外，mTBI减缓了AMPAR电流的衰减时间，缩短了GABAAR电流的衰减时间，表明mTBI改变了AMPAR和GABAAR亚基组成。另一方面，mTBI降低了sEPSCs的频率，同时增强了sIPSCs的频率，导致mTBI动物CA1锥体神经元中sEPSC/sIPSC频率比低于假动物。总之，我们的研究结果表明，mTBI诱导了CA1神经元中AMPAR和GABAAR功能及其突触组成的持续突触后改变，同时引发了突触前驱动的兴奋/抑制（E/I）平衡向海马CA1细胞抑制性突触驱动的代偿性转移。持续的mTBI诱导的CA1突触功能障碍和E/I失衡可能导致海马可塑性缺陷，这是mTBI患者在初始损伤后很长时间内长期海马依赖学习和记忆缺陷的基础。
Mild traumatic brain injury (mTBI) or concussion is the most common form of TBI which frequently results in persistent cognitive impairments and memory deficits in affected individuals [1]. Although most studies have investigated the role of hippocampal synaptic dysfunction in earlier time points following a single injury, the long-lasting effects of mTBI on hippocampal synaptic transmission following multiple brain concussions have not been well-elucidated. Using a repetitive closed head injury (3XCHI) mouse model of mTBI, we examined the alteration of spontaneous synaptic transmission onto hippocampal CA1 pyramidal neurons by recording spontaneous excitatory AMPA receptor (AMPAR)- and inhibitory GABAAR-mediated postsynaptic currents (sEPSCs and sIPSCs, respectively) in adult male mice 2-weeks following the injury. We found that mTBI potentiated postsynaptic excitatory AMPAR synaptic function while depressed postsynaptic inhibitory GABAAR synaptic function in CA1 pyramidal neurons. Additionally, mTBI slowed the decay time of AMPAR currents while shortened the decay time of GABAAR currents suggesting changes in AMPAR and GABAAR subunit composition by mTBI. On the other hand, mTBI reduced the frequency of sEPSCs while enhanced the frequency of sIPSCs resulting in a lower ratio of sEPSC/sIPSC frequency in CA1 pyramidal neurons of mTBI animals compared to sham animals. Altogether, our results suggest that mTBI induces persistent postsynaptic modifications in AMPAR and GABAAR function and their synaptic composition in CA1 neurons while triggering a compensatory shift in excitation/inhibition (E/I) balance of presynaptic drives towards more inhibitory synaptic drive to hippocampal CA1 cells. The persistent mTBI-induced CA1 synaptic dysfunction and E/I imbalance could contribute to deficits in hippocampal plasticity that underlies long-term hippocampal-dependent learning and memory deficits in mTBI patients long after the initial injury.
登录
查看更多内容
影响因子：
3.3
作者：
Pavlov, I.;Huusko, N.;Walker, M. C.
通讯作者：
Walker, M. C.
影响因子：
3.7
作者：
Hehar, Harleen;Yeates, Keith;Mychasiuk, Richelle
通讯作者：
Mychasiuk, Richelle
影响因子：
3.5
作者：
Schwarzbach, E.;Bonislawski, D. P.;Cohen, A. S.
通讯作者：
Cohen, A. S.
影响因子：
4.2
作者：
Schneider, Brandy L.;Ghoddoussi, Farhad;Conti, Alana C.
通讯作者：
Conti, Alana C.
影响因子：
4.2
作者：
Selvaraj, Prabhuanand;Wen, Jie;Zhang, Yumin
通讯作者：
Zhang, Yumin