Use-dependent synaptic plasticity associates with modulation of blood-brain-barrier permeability in the somatosensory cortex

The effect of neuronal activity on blood-brain barrier function and whether it plays a role in plasticity in the healthy brain remains unclear. We show that neuronal activity induces modulation of microvascular permeability in the healthy brain and that it has a role in local network reorganization. Combining simultaneous electrophysiological recording and vascular imaging with transcriptomic analysis in rats, and functional and BBB-mapping MRI in human subjects we show that prolonged stimulation of the limb induces a focal increase in BBB permeability in the corresponding somatosensory cortex that is associated with long-term synaptic plasticity. We further show that the increased microvascular permeability depends on neuronal activity and involves caveolae-mediated transcytosis and transforming growth factor beta signaling. Our results reveal a role of BBB modulation in cortical plasticity in the healthy brain, highlighting the importance of neurovascular interactions for sensory experience and learning. Overall design: Bulk RNA-sequencing of rat sensorimotor cortex contralateral and ipsilateral to the stimulated limb. Tissue was harvested 1 hour and 24 hour post-stimulation for transcriptomic analysis of differentially expressed genes in the contralateral (“stimulated”) compared to the ipsilateral (“non-stimulated”) cortex. Corresponding striatum samples were likewise dissected and sequenced for RNA-sequencing validation and reference control.