Department of Neurobiology, Physiology, and Behavior, University of California, Davis, CA 95616.
INSERM U894, Team Synaptic Plasticity and Neural Networks, Université Paris Descartes, Paris 75014, France.
eNeuro. 2017 Aug 24;4(4). doi: 10.1523/ENEURO.0267-17.2017. eCollection 2017 Jul-Aug.
The CA1 region of the hippocampus plays a critical role in spatial and contextual memory, and has well-established circuitry, function and plasticity. In contrast, the properties of the flanking CA2 pyramidal neurons (PNs), important for social memory, and lacking CA1-like plasticity, remain relatively understudied. In particular, little is known regarding the expression of voltage-gated K (Kv) channels and the contribution of these channels to the distinct properties of intrinsic excitability, action potential (AP) waveform, firing patterns and neurotransmission between CA1 and CA2 PNs. In the present study, we used multiplex fluorescence immunolabeling of mouse brain sections, and whole-cell recordings in acute mouse brain slices, to define the role of heterogeneous expression of Kv2 family Kv channels in CA1 versus CA2 pyramidal cell excitability. Our results show that the somatodendritic delayed rectifier Kv channel subunits Kv2.1, Kv2.2, and their auxiliary subunit AMIGO-1 have region-specific differences in expression in PNs, with the highest expression levels in CA1, a sharp decrease at the CA1-CA2 boundary, and significantly reduced levels in CA2 neurons. PNs in CA1 exhibit a robust contribution of Guangxitoxin-1E-sensitive Kv2-based delayed rectifier current to AP shape and after-hyperpolarization potential (AHP) relative to that seen in CA2 PNs. Our results indicate that robust Kv2 channel expression confers a distinct pattern of intrinsic excitability to CA1 PNs, potentially contributing to their different roles in hippocampal network function.
海马体的 CA1 区域在空间和情景记忆中起着关键作用，其具有成熟的回路、功能和可塑性。相比之下，侧翼 CA2 锥体神经元（PNs）的特性对于社会记忆很重要，并且缺乏 CA1 样的可塑性，这方面的研究仍然相对较少。特别是，对于电压门控 K（Kv）通道的表达以及这些通道对内在兴奋性、动作电位（AP）波形、放电模式和 CA1 与 CA2 PNs 之间神经递质传递的独特特性的贡献知之甚少。在本研究中，我们使用了小鼠脑切片的多重荧光免疫标记和急性小鼠脑切片的全细胞记录，以确定 Kv2 家族 Kv 通道的异质表达在 CA1 与 CA2 锥体神经元兴奋性中的作用。我们的结果表明，Kv2.1、Kv2.2 和它们的辅助亚基 AMIGO-1 等位于树突体的延迟整流性 Kv 通道亚基在 PNs 中的表达具有区域特异性差异，在 CA1 中的表达水平最高，在 CA1-CA2 边界处急剧下降，而在 CA2 神经元中的表达水平显著降低。与 CA2 PNs 相比，CA1 中的 PN 表现出 Guangxitoxin-1E 敏感的基于 Kv2 的延迟整流电流对 AP 形状和后超极化电位（AHP）的强烈贡献。我们的结果表明，强大的 Kv2 通道表达赋予 CA1 PNs 独特的内在兴奋性模式，可能有助于它们在海马体网络功能中发挥不同的作用。
