Unilateral traumatic brain injury (TBI) causes cortical dysfunctions spreading to the primarily undamaged hemisphere. This phenomenon, called transhemispheric diaschisis, is mediated by an imbalance of glutamatergic versus GABAergic neurotransmission. This study investigated the role of GABAergic, somatostatin-positive (SST) interneurons in the contralateral hemisphere 72 h after unilateral TBI. The brain injury was induced to the primary motor/somatosensory cortex of glutamate decarboxylase 67–green fluorescent protein (GAD67-GFP) knock-in mice at postnatal days 19–21 under anesthesia in vivo. Single GFP+ interneurons of the undamaged, contralateral cortex were isolated by fluorescence-activated cell sorting and analyzed by mass spectrometry. TBI caused a switch of 2 α subunits of pore-forming L-type voltage-gated calcium channels (VGCC) in GABAergic interneurons, an increased expression of CaV1.3, and simultaneous ablation of CaV1.2. This switch was associated with 1) increased excitability of single SST interneurons in patch-clamp recordings and (2) a recovery from early network hyperactivity in the contralateral hemisphere in microelectrode array recordings of acute slices. The electrophysiological changes were sensitive to pharmacological blockade of CaV1.3 (isradipine, 100 nM). These data identify a switch of 2 α subunits of VGCCs in SST interneurons early after TBI as a mechanism to counterbalance post-traumatic hyperexcitability.

中文翻译：

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L型电压门控钙通道α亚基转换对脑外伤后生长抑素阳性中间神经元的适应性机制

单侧创伤性脑损伤 (TBI) 导致皮质功能障碍扩散到主要未受损的半球。这种现象称为跨半球神经功能障碍，是由谷氨酸能与 GABA 能神经传递的失衡介导的。本研究调查了单侧 TBI 后 72 小时 GABA 能、生长抑素阳性 (SST) 中间神经元在对侧半球中的作用。在体内麻醉下，在出生后第 19-21 天，谷氨酸脱羧酶 67-绿色荧光蛋白 (GAD67-GFP) 敲入小鼠的初级运动/躯体感觉皮层被诱导脑损伤。通过荧光激活细胞分选分离未损坏的对侧皮质的单个 GFP+ 中间神经元，并通过质谱分析。TBI 导致 GABAergic 中间神经元中成孔 L 型电压门控钙通道 (VGCC) 的 2 个 α 亚基转换，CaV1.3 表达增加，同时消除 CaV1.2。此开关与 1) 膜片钳记录中单个 SST 中间神经元的兴奋性增加和 (2) 急性切片微电极阵列记录中对侧半球早期网络过度活跃的恢复有关。电生理变化对 CaV1.3（伊拉地平，100 nM）的药理学阻断敏感。这些数据确定了 TBI 后早期 SST 中间神经元中 VGCC 的 2 个 α 亚基的转换，作为平衡创伤后过度兴奋的机制。此开关与 1) 膜片钳记录中单个 SST 中间神经元的兴奋性增加和 (2) 急性切片微电极阵列记录中对侧半球早期网络过度活跃的恢复有关。电生理变化对 CaV1.3（伊拉地平，100 nM）的药理学阻断敏感。这些数据确定了 TBI 后早期 SST 中间神经元中 VGCC 的 2 个 α 亚基的转换，作为平衡创伤后过度兴奋的机制。此开关与 1) 膜片钳记录中单个 SST 中间神经元的兴奋性增加和 (2) 急性切片微电极阵列记录中对侧半球早期网络过度活跃的恢复有关。电生理变化对 CaV1.3（伊拉地平，100 nM）的药理学阻断敏感。这些数据确定了 TBI 后早期 SST 中间神经元中 VGCC 的 2 α 亚基的转换，作为平衡创伤后过度兴奋的机制。