Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance

• 成果类型: Article
• 署名作者: Jiang-Xie, Li-Feng; Drieu, Antoine; Bhasiin, Kesshni; Quintero, Daniel; Smirnov, Igor; Kipnis, Jonathan
• 署名单位: Washington University (WUSTL); Washington University (WUSTL)
• 刊物名称: Nature
• ISSN/ISSBN: 0028-3856
• DOI: 10.1038/s41586-024-07108-6
• 发表日期: 2024-03-07
• 页码: 157-164
• 关键词: slow oscillation; sleep; anesthesia; waves

摘要

The accumulation of metabolic waste is a leading cause of numerous neurological disorders, yet we still have only limited knowledge of how the brain performs self-cleansing. Here we demonstrate that neural networks synchronize individual action potentials to create large-amplitude, rhythmic and self-perpetuating ionic waves in the interstitial fluid of the brain. These waves are a plausible mechanism to explain the correlated potentiation of the glymphatic flow(1,2) through the brain parenchyma. Chemogenetic flattening of these high-energy ionic waves largely impeded cerebrospinal fluid infiltration into and clearance of molecules from the brain parenchyma. Notably, synthesized waves generated through transcranial optogenetic stimulation substantially potentiated cerebrospinal fluid-to-interstitial fluid perfusion. Our study demonstrates that neurons serve as master organizers for brain clearance. This fundamental principle introduces a new theoretical framework for the functioning of macroscopic brain waves.