CaV3.1 T-type calcium channels are important for spatial memory processing in the dorsal subiculum.
CaV3.1 T-type calcium channels are important for spatial memory processing in the dorsal subiculum.
复制标题
CaV3.1 T 型钙通道对于背下托的空间记忆处理很重要。
DOI：
10.1016/j.neuropharm.2022.109400
复制
发表时间：
2023
影响因子：
4.7
通讯作者：
Todorovic,SlobodanM
中科院分区：
文献类型：
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作者：
Joksimovic,SrdjanM;Ghodsi,SeyedMohammadreza;Heinsbroek,JasperA;Orfila,JamesE;Busquet,Nicolas;Tesic,Vesna;Valdez,Robert;Fine-Raquet,Brier;Jevtovic-Todorovic,Vesna;Raol,YogendraH;Herson,PacoS;Todorovic,SlobodanM
背侧下托（dorsal subiculum，dSub）是海马记忆痕迹形成的关键结构之一，但单个离子电流对其认知功能的影响还没有得到很好的研究。尽管我们最近报道了低电压激活的T型钙通道（T-channels）在dSub锥体神经元的爆发放电模式调节中起关键作用，但其在学习和记忆中的潜在作用仍不清楚。在这里，我们使用自由行为的小鼠体内局部场电位记录和微型钙成像，结合药理学和遗传学工具来解决这一知识空白。我们表明，CaV3.1亚型的T-通道是至关重要的参与控制神经元活动的dSub体内。通过抑制T-通道活性改变神经元兴奋性显著影响钙动力学、突触可塑性、神经元振荡和dSub中的相位-振幅耦合，从而破坏空间学习。这些结果提供了一个重要的CaV3.1通道，dSub神经元的突发放电和记忆形成之间的因果关系，从而进一步支持的概念，神经元兴奋性的变化调节记忆处理。我们认为，下丘CaV3.1 T通道可能是一个有前途的新的药物靶点的认知障碍。
The dorsal subiculum (dSub) is one of the key structures responsible for the formation of hippocampal memory traces but the contribution of individual ionic currents to its cognitive function is not well studied. Although we recently reported that low-voltage-activated T-type calcium channels (T-channels) are crucial for the burst firing pattern regulation in the dSub pyramidal neurons, their potential role in learning and memory remains unclear. Here we usedin vivolocal field potential recordings and miniscope calcium imaging in freely behaving mice coupled with pharmacological and genetic tools to address this gap in knowledge. We show that the CaV3.1 isoform of T-channels is critically involved in controlling neuronal activity in the dSubin vivo. Altering neuronal excitability by inhibiting T-channel activity markedly affects calcium dynamics, synaptic plasticity, neuronal oscillations and phase-amplitude coupling in the dSub, thereby disrupting spatial learning. These results provide an important causative link between the CaV3.1 channels, burst firing of dSub neurons and memory formation, thus further supporting the notion that changes in neuronal excitability regulate memory processing. We posit that subicular CaV3.1 T-channels could be a promising novel drug target for cognitive disorders.