Cognition and behavior, Neuronal circuits, neurophysiology and optogenetic approaches

Publication date: 06/02/2025

Authors: Natalie L. Hauglund, Mie Andersen, Klaudia Tokarska, ..., Pia Weikop, Hajime Hirase, Maiken Nedergaard

Journal: Cell

Commentary: A groundbreaking study in Cell reveals that slow oscillations in norepinephrine (NE) during non-REM (NREM) sleep are key to activating the brain’s glymphatic system—a waste clearance pathway. Researchers used innovative fiber photometry to monitor NE, blood flow, and cerebrospinal fluid (CSF) dynamics in freely moving mice. They discovered that NE released from the locus coeruleus triggers rhythmic constriction and dilation of blood vessels (vasomotion), which in turn pumps CSF through the brain to remove metabolic waste. Optogenetic stimulation of NE release enhanced clearance, while the sleep aid zolpidem disrupted NE oscillations and suppressed glymphatic flow. These findings explain how brain clearance is orchestrated during sleep and suggest that preserving natural NE rhythms may be critical for preventing neurodegenerative diseases. The study also questions the efficacy of certain sleep medications in supporting restorative brain functions.

Commented by: Stefano Raffaele (29/05/2025)

DOI: https://doi.org/10.1016/j.cell.2024.11.027