ORIGINAL RESEARCH article

Front. Aging Neurosci.

Sec. Cellular and Molecular Mechanisms of Brain-aging

Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1573906

This article is part of the Research TopicUnraveling the Mysteries of Aging and the Brain: Advancements in Understanding Neurodegenerative Diseases & DementiaView all 6 articles

Vulnerability of Long-range inputome of Basal Forebrain in Normal Aging Mice

Provisionally accepted
  • 1Huazhong University of Science and Technology, Wuhan, China
  • 2Hainan University, Haikou, Hainan Province, China

The final, formatted version of the article will be published soon.

As the human undergoes the process of aging, it becomes evident that the elderly population exhibits age-related cognitive decline. The basal forebrain (BF) has been shown to have complex connections with the hippocampus (Hip) and medial prefrontal cortex (mPFC) through circuits, and is involved in cognitive functions. However, which circuit is most vulnerable during normal aging remains unclear. Here, utilizing a combination of viral tracing and fluorescence micro-optical sectioning tomography (fMOST), we performed quantitative analyses on the whole-brain inputs of the BF, Hip, and mPFC during normal aging. The long-range inputome revealed that the nucleus of the diagonal band (NDB) of BF was vulnerability to damage, especially the connection strength of the vCA3-NDB circuit is significantly reduced, which may be related to decision making. A comparison of the 3D continuous data of BF subregions revealed that aging resulted in a weakened connection strength between each region and the olfactory areas (OLF), which obeyed a topological relationship, which might be related to the learning and memory. These results provide an anatomical foundation for understanding the selective vulnerability of BF circuit during normal aging and offer a novel perspective for future research into the treatment of age-related cognitive decline.

Keywords: basal forebrain, long-range input, Normal ageing, Whole Brain, three-dimensional

Received: 10 Feb 2025; Accepted: 09 Jul 2025.

Copyright: © 2025 Sun, Chen, Liu, Li, Gong and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Xiangning Li, Hainan University, Haikou, 570228, Hainan Province, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.