Intercellular communication in the brain through a dendritic nanotubular network

Abstract

Intercellular nanotubular networks mediate material exchange, but their existence in neurons remains to be explored in detail. We identified long, thin dendritic filopodia forming direct dendrite–dendrite nanotubes (DNTs) in mammalian cortex. Super-resolution microscopy in dissociated neurons revealed DNTs’ actin-rich composition and dynamics, enabling long-range calcium ion (Ca²⁺) propagation. Imaging and machine learning–based analysis validated in situ DNTs as anatomically distinct from synaptic spines. DNTs actively transported small molecules and human amyloid-β (Aβ); DNT density increased before plaque formation in the medial prefrontal cortex of APP/PS1 mice (APP, Aβ precursor protein; PS1, presenilin-1), suggesting that the dendrite-DNT network might play a role in Alzheimer’s disease pathology. Computational models of DNT-mediated Aβ propagation recapitulated early amyloidosis, predicting selective intracellular accumulation. These findings uncover a nanotubular connectivity layer in the brain, extending neuronal communication beyond classical synapses.