Incontro Salvatore, Sandoval-Burnside Janaie, Guo Lijun, Clark Colin, Dryden Miles, Kazimuddin Simra, Nguyen Quynh-Anh
Department of Pharmacology, Vanderbilt University, Nashville, TN 37240-7933.
Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232-2050.
bioRxiv. 2025 Aug 18:2025.08.13.670170. doi: 10.1101/2025.08.13.670170.
The fasciola cinereum (FC) is a small, conserved hippocampal subregion whose function has remained largely unexplored. Anatomically situated between dorsal CA1 and the third ventricle in rodents, the FC receives diverse cortical and subcortical inputs yet is often omitted from hippocampal circuit models. There remains a fundamental knowledge gap regarding the cell types and intrinsic properties of neurons in FC and whether they are distinct from neighboring hippocampal subregions. Here, we performed whole-cell patch-clamp recordings in mouse hippocampal slices to characterize FC neurons. We found that FC cells are functionally distinct from neighboring CA1 pyramidal cells, exhibiting significantly reduced excitability, delayed spike initiation, and enhanced afterhyperpolarization (AHP) currents, consistent with strong potassium conductance. Notably, we identified two electrophysiologically distinguishable FC neuron excitatory cell subtypes, differing in excitability and potassium channel activity. Pharmacological analyses demonstrated that Kv2.1 and Kv7 potassium channels play a key role in shaping the intrinsic properties of FC neurons, underlying their reduced excitability. These findings suggest that the FC is a heterogeneous structure, molecularly and functionally specialized for gating excitability within the hippocampal circuit.
灰被(FC)是一个小的、保守的海马亚区,其功能在很大程度上尚未得到探索。在啮齿动物中,FC在解剖学上位于背侧CA1和第三脑室之间,它接收多种皮质和皮质下输入,但在海马回路模型中常常被忽略。关于FC中神经元的细胞类型和内在特性,以及它们是否与相邻的海马亚区不同,仍然存在基本的知识空白。在这里,我们在小鼠海马切片中进行了全细胞膜片钳记录,以表征FC神经元。我们发现,FC细胞在功能上与相邻的CA1锥体细胞不同,表现出明显降低的兴奋性、延迟的动作电位起始和增强的超极化后电流(AHP),这与强大的钾电导一致。值得注意的是,我们鉴定出两种在电生理上可区分的FC神经元兴奋性细胞亚型,它们在兴奋性和钾通道活性方面存在差异。药理学分析表明,Kv2.1和Kv7钾通道在塑造FC神经元的内在特性方面起关键作用,这是其兴奋性降低的基础。这些发现表明,FC是一个异质性结构,在分子和功能上专门用于调节海马回路中的兴奋性。