O'Reilly Kally C, Flatberg Arnar, Islam Sobia, Olsen Lene C, Kruge Ingvild Ulsaker, Witter Menno P
Kavli Institute for Systems Neuroscience, Centre for Neural Computation, Medical Technical Research Centre, Norwegian University of Science and Technology, Postboks 8905, 7491, Trondheim, Norway,
Brain Struct Funct. 2015 Sep;220(5):2873-93. doi: 10.1007/s00429-014-0831-8. Epub 2014 Jul 11.
The adult hippocampal formation (HF) is functionally, connectionally, and transcriptionally differentiated along the dorsal-ventral axis. At birth, the hippocampus appears shortened along its dorsal-ventral axis. We therefore questioned at what postnatal age the differentiated dorsal-ventral hippocampus is present. We first established that the ventral tissue in the short postnatal hippocampus remains ventral in the adult-like hippocampus. Second, using anatomical tracing techniques we report that, within the first postnatal week, the main input from the entorhinal cortex (EC) to HF is topographically organized. The terminal distribution of this input along the dorsal-ventral axis of HF was related to a dorsolateral-to-ventromedial axis of origin in EC, thus reflecting adult topography. Finally, we examined gene expression along the dorsal-ventral axis in the developing hippocampus. We found that several genes that were differentially enriched in the adult dorsal and ventral hippocampus were similarly enriched in the dorsal and ventral hippocampal poles at birth. The differentially expressed genes relate to different molecular pathways and biomarkers of disease. Taken together, these data lead us to conclude that the entire dorsal-ventral axis of HF is present at birth showing adult-like functional differentiation. Moreover, our findings indicate that the neonatal ventral hippocampus is enriched with biomarkers associated with mental illnesses. These include schizophrenia, affective and anxiety disorders, disorders previously deemed as ventral hippocampal associated disorders, as well as alcoholism. Our results thus suggest an early developmental susceptibility of the ventral HF to mental illness.
成年海马结构（HF）在功能、连接和转录方面沿背腹轴存在差异。出生时，海马在其背腹轴上显得缩短。因此，我们质疑在出生后哪个年龄段出现分化的背腹海马。我们首先确定出生后短海马中的腹侧组织在成年样海马中仍为腹侧。其次，使用解剖追踪技术我们报告，在出生后的第一周内，内嗅皮质（EC）到HF的主要输入在拓扑学上是有组织的。这种输入沿HF背腹轴的终末分布与EC中从背外侧到腹内侧的起源轴相关，从而反映了成年时的拓扑结构。最后，我们检查了发育中海马背腹轴上的基因表达。我们发现，在成年背侧和腹侧海马中差异富集的几个基因在出生时的背侧和腹侧海马极中也同样富集。这些差异表达的基因与不同的分子途径和疾病生物标志物有关。综合这些数据，我们得出结论，HF的整个背腹轴在出生时就已存在，并表现出成年样的功能分化。此外，我们的研究结果表明，新生腹侧海马富含与精神疾病相关的生物标志物。这些疾病包括精神分裂症、情感和焦虑障碍、以前被认为是腹侧海马相关的疾病以及酒精中毒。因此，我们的结果表明腹侧HF在发育早期对精神疾病易感。
