Hidden networks in the brain

Intercellular communication is essential in multicellular organisms. Cells communicate through direct contact, using ligand-receptor interactions, and through the release of extracellular vesicles and diffusible messengers (1). Yet, there is also a more elusive form of intercellular connectivity: thin membranous bridges that allow the direct transfer of ions, proteins, and organelles (2). Known as tunneling nanotubes (TNTs), these structures can connect immune cells (3), cancer cells (4), and stem cells (5), among others (6). However, their presence in the mammalian brain has remained difficult to prove. On page 43 of this issue, Chang et al. (7) report the observation of dendritic nanotubes (DNTs) in brain tissue from mice and humans. These thin, actin-based protrusions form bridges between neurons, transmitting calcium signals and even amyloid-β (Aβ), a key protein in Alzheimer’s disease (AD) pathology. The discovery suggests that the current understanding of the brain’s organization may be incomplete, overlooking a hidden layer of connectivity.