Hippocampal interneuronal dysfunction and hyperexcitability in a porcine model of concussion.
Hippocampal interneuronal dysfunction and hyperexcitability in a porcine model of concussion.
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DOI：
10.1038/s42003-023-05491-w
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发表时间：
2023-11-09
影响因子：
5.9
通讯作者：
Wolf, John A
中科院分区：
文献类型：
--
作者：
Ulyanova, Alexandra V;Adam, Christopher D;Cottone, Carlo;Maheshwari, Nikhil;Grovola, Michael R;Fruchet, Oceane E;Alamar, Jami;Koch, Paul F;Johnson, Victoria E;Cullen, D Kacy;Wolf, John A
认知障碍是轻度创伤性脑损伤（mTBI 或脑震荡）后的常见症状，并且在某些个体中可能持续数年。猪闭头旋转加速损伤后的海马切片制备先前已证明轴突功能降低和海马回路破坏。然而，大型动物 mTBI 模型中海马神经元及其亚型的电生理变化尚未得到研究。使用体内电生理学技术，我们检查了麻醉小型猪受伤后 7 天海马网络中的层流振荡场电位和单个单元活动。震荡改变了 CA1 区锥体细胞和中间神经元的电生理特性。虽然 mTBI 后 CA1 中间神经元的放电率、尖峰宽度和振幅显着降低，但 CA1 锥体神经元中的这些参数没有变化。此外，TBI 动物的 CA1 锥体神经元较少受到海马伽马 (40–80Hz) 振荡的影响。对 Schaffer 络脉的刺激也揭示了 mTBI 后 CA1 层的过度兴奋。计算模拟表明，所报道的神经元间生理学变化可能是由于电压门控钠通道的变化所致。这些数据表明，单次脑震荡可导致海马体神经元和回路水平发生显着变化，这可能导致 mTBI 后的认知功能障碍。猪的体内细胞外记录显示，脑震荡优先破坏海马中间神经元的活动，导致网络过度兴奋，计算机模型表明电压门控钠通道动力学发生改变。
Cognitive impairment is a common symptom following mild traumatic brain injury (mTBI or concussion) and can persist for years in some individuals. Hippocampal slice preparations following closed-head, rotational acceleration injury in swine have previously demonstrated reduced axonal function and hippocampal circuitry disruption. However, electrophysiological changes in hippocampal neurons and their subtypes in a large animal mTBI model have not been examined. Using in vivo electrophysiology techniques, we examined laminar oscillatory field potentials and single unit activity in the hippocampal network 7 days post-injury in anesthetized minipigs. Concussion altered the electrophysiological properties of pyramidal cells and interneurons differently in area CA1. While the firing rate, spike width and amplitude of CA1 interneurons were significantly decreased post-mTBI, these parameters were unchanged in CA1 pyramidal neurons. In addition, CA1 pyramidal neurons in TBI animals were less entrained to hippocampal gamma (40–80 Hz) oscillations. Stimulation of the Schaffer collaterals also revealed hyperexcitability across the CA1 lamina post-mTBI. Computational simulations suggest that reported changes in interneuronal physiology may be due to alterations in voltage-gated sodium channels. These data demonstrate that a single concussion can lead to significant neuronal and circuit level changes in the hippocampus, which may contribute to cognitive dysfunction following mTBI. In vivo extracellular recordings in pigs reveal that concussion preferentially disrupts the activity of hippocampal interneurons leading to network hyperexcitability, with in silico models implicating altered voltage-gated sodium channel kinetics.