Ishihara Yoshihisa, Miyamoto Yuta, Esumi Shigeyuki, Fukuda Takaichi
Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Department of Molecular Anatomy, School of Medicine, University of the Ryukyus, Uehara, Nishihara Cho, Nakagami Gun, Okinawa Ken, 903-0125, Japan.
Anat Sci Int. 2025 Mar;100(2):207-227. doi: 10.1007/s12565-024-00803-4. Epub 2024 Oct 4.
The subiculum is one of the major output structures of the hippocampal formation and is an important brain region for memory. We have previously reported that the subiculum of rodents can be morphologically divided into its temporal (ventral) two-thirds and the septal (dorsal) third and that the former can be further subdivided into the distal (Sub1) and proximal (Sub2) regions, on a basis of immunohistochemical localizations of several Sub2-specific proteins. However, it remains unclear whether detailed structural organization found in the temporal subiculum is applicable to the septal subiculum. In this study, we found that the distribution of fibronectin (FN1)-positive non-GABAergic, presumptive pyramidal cells exactly coincided with the extent of the Sub1 region of male mice. Using FN1 immunohistochemistry, the Sub1 was found to keep relatively constant size throughout the septotemporal axis of the subiculum. In contrast, the size of the Sub2 became smaller as it approached the septal side, and the Sub2 finally disappeared at the most septal level of the subiculum. Retrograde tracer experiments confirmed that FN1-positive Sub1 neurons projected to the retrosplenial cortex, which is thought to be associated with spatial memory, whereas FN1-negative Sub2 neurons projected to the nucleus accumbens associated with emotional memory. Considering both the functional segregation of these two subicular targets and the relative abundance of the Sub2 on the temporal side, the subiculum can be one of the neural substrates for functional differences between the septal and temporal hippocampal formation associated with the spatial and emotional memory, respectively.
海马下脚是海马结构的主要输出结构之一，是记忆的重要脑区。我们之前报道过，啮齿动物的海马下脚在形态上可分为颞侧（腹侧）三分之二和隔侧（背侧）三分之一，并且基于几种海马下脚2区特异性蛋白的免疫组化定位，前者可进一步细分为远端（Sub1）和近端（Sub2）区域。然而，颞侧海马下脚中发现的详细结构组织是否适用于隔侧海马下脚仍不清楚。在本研究中，我们发现纤连蛋白（FN1）阳性的非GABA能、推测为锥体细胞的分布与雄性小鼠Sub1区域的范围完全一致。利用FN1免疫组化，发现Sub1在海马下脚的整个隔颞轴上保持相对恒定的大小。相比之下，Sub2的大小在靠近隔侧时变小，最终在海马下脚最隔侧的水平消失。逆行示踪实验证实，FN1阳性的Sub1神经元投射到与空间记忆相关的 retrosplenial 皮质，而FN1阴性的Sub2神经元投射到与情绪记忆相关的伏隔核。考虑到这两个海马下脚靶点的功能分离以及颞侧Sub2的相对丰富性，海马下脚可能是分别与空间和情绪记忆相关的隔侧和颞侧海马结构功能差异的神经基础之一。
