Laboratory of Cellular Neuropharmacology, Institute of Experimental Medicine, Budapest, Hungary.
János Szentágothai School of Neurosciences, Semmelweis University, Budapest, Hungary.
Elife. 2020 Jun 3;9:e58515. doi: 10.7554/eLife.58515.
CCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity. We found two firing phenotypes of CCK+INs in rat hippocampal CA3 area; either possessing a previously undetected membrane potential-dependent firing or regular firing phenotype, due to different low-voltage-activated potassium currents. These different excitability properties destine the two types for distinct functions, because the former is essentially silenced during realistic 8-15 Hz oscillations. By contrast, the general intrinsic excitability, morphology and gene-profiles of the two types were surprisingly similar. Even the expression of Kv4.3 channels were comparable, despite evidences showing that Kv4.3-mediated currents underlie the distinct firing properties. Instead, the firing phenotypes were correlated with the presence of distinct isoforms of Kv4 auxiliary subunits (KChIP1 vs. KChIP4e and DPP6S). Our results reveal the underlying mechanisms of two previously unknown types of CCK+INs and demonstrate that alternative splicing of few genes, which may be viewed as a minor change in the cells' whole transcriptome, can determine cell-type identity.
表达胆囊收缩素的中间神经元（CCK+INs）对于控制海马体活动至关重要。我们在大鼠海马体 CA3 区发现了两种 CCK+IN 的放电表型；一种具有以前未检测到的膜电位依赖性放电，另一种具有规则放电表型，这是由于不同的低电压激活钾电流所致。这些不同的兴奋性特性决定了这两种类型具有不同的功能，因为前者在现实的 8-15Hz 振荡中基本上处于沉默状态。相比之下，这两种类型的内在兴奋性、形态和基因特征惊人地相似。即使 Kv4.3 通道的表达也相当相似，尽管有证据表明 Kv4.3 介导的电流是产生不同放电特性的基础。相反，放电表型与 Kv4 辅助亚基（KChIP1 与 KChIP4e 和 DPP6S）的不同异构体的存在相关。我们的研究结果揭示了两种以前未知类型的 CCK+INs 的潜在机制，并证明了少数基因的选择性剪接，这些基因可能被视为细胞整个转录组中的微小变化，可以决定细胞类型的身份。
