Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
J Neurophysiol. 2020 Oct 1;124(4):1270-1284. doi: 10.1152/jn.00147.2020. Epub 2020 Sep 16.
Area CA3 in the hippocampus is traditionally thought to act as a homogeneous neural circuit that is vital for spatial navigation and episodic memories. However, recent studies have revealed that CA3 pyramidal neurons in dorsal hippocampus display marked anatomic and functional heterogeneity along the proximodistal (transverse) axis. The hippocampus is also known to be functionally segregated along the dorsoventral (longitudinal) axis, with dorsal hippocampus strongly involved in spatial navigation and ventral hippocampus associated with emotion and anxiety. Surprisingly, however, relatively little is known about CA3 functional heterogeneity along the dorsoventral axis. Here, we carried out mouse-brain-slice patch-clamp recordings and morphological analyses to examine the heterogeneity of CA3 cellular properties along both proximodistal and dorsoventral axes. We find that CA3 pyramidal neurons exhibit considerable heterogeneity of somatodendritic morphology and intrinsic membrane properties, with ventral CA3 (vCA3) displaying more elaborate somatodendritic morphology, lower intrinsic excitability, smaller input resistance, greater cell capacitance, and more prominent hyperpolarization-activated current than dorsal CA3 (dCA3). Furthermore, although both dCA3 and vCA3 exhibit proximal-to-distal gradients in intrinsic properties and neuronal morphology, these proximal-to-distal gradients in vCA3 are more moderate than those in dCA3. Taken together, our results extend previous findings on the proximodistal heterogeneity of dCA3 function and uncover a complex, yet orderly, pattern of topographic organization of CA3 neuronal features that extends to multiple anatomic dimensions and may contribute to its in vivo functional diversity. Area CA3 is a major hippocampal region that is classically thought to act as a homogeneous neural network vital for spatial navigation and episodic memories. Here, we report that CA3 pyramidal neurons exhibit marked heterogeneity of somatodendritic morphology and cellular electrical properties along both proximodistal and dorsoventral axes. These new results uncover a complex, yet orderly, pattern of topographic organization of CA3 neuronal features that may contribute to its in vivo functional diversity.
CA3 区在海马体中传统上被认为是一个同质的神经网络，对空间导航和情景记忆至关重要。然而，最近的研究表明，背侧海马 CA3 锥体神经元在近-远轴（横向）上表现出明显的解剖和功能异质性。海马体也被认为是沿着背-腹轴（纵向）功能上分离的，背侧海马体强烈参与空间导航，腹侧海马体与情绪和焦虑相关。然而，令人惊讶的是，人们对 CA3 沿着背-腹轴的功能异质性知之甚少。在这里，我们进行了小鼠脑片膜片钳记录和形态学分析，以研究 CA3 细胞特性在近-远和背-腹轴上的异质性。我们发现 CA3 锥体神经元在树突体形态和内在膜特性上表现出相当大的异质性，腹侧 CA3（vCA3）显示出更精细的树突体形态，内在兴奋性更低，输入电阻更大，细胞电容更大，超极化激活电流更明显比背侧 CA3（dCA3）。此外，尽管 dCA3 和 vCA3 都表现出内在特性和神经元形态的近-远梯度，但 vCA3 的近-远梯度比 dCA3 的更温和。总的来说，我们的结果扩展了以前关于 dCA3 功能近-远异质性的发现，并揭示了 CA3 神经元特征的复杂但有序的地形组织模式，这种模式延伸到多个解剖维度，可能有助于其体内功能多样性。CA3 区是海马体的一个主要区域，传统上被认为是一个同质的神经网络，对空间导航和情景记忆至关重要。在这里，我们报告 CA3 锥体神经元在近-远和背-腹轴上表现出明显的树突体形态和细胞电特性的异质性。这些新的结果揭示了 CA3 神经元特征的复杂但有序的地形组织模式，这可能有助于其体内功能多样性。
