Cortical plasticity is associated with blood–brain barrier modulation

• Published in: eLife Vol. 12
• Main Authors: Swissa, Evyatar, Monsonego, Uri, Yang, Lynn T, Schori, Lior, Kamintsky, Lyna, Mirloo, Sheida, Burger, Itamar, Uzzan, Sarit, Patel, Rishi, Sudmant, Peter H, Prager, Ofer, Kaufer, Daniela, Friedman, Alon
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 18.07.2024; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Adult; Albumin; Animals; Blood-Brain Barrier; Brain; Brain injury; Brain mapping; Capillary Permeability; Caveolae; caveolae-mediated transcytosis; Electrophysiological recording; Excitability; Functional magnetic resonance imaging; Functional plasticity; Growth factors; Hemoglobin; Humans; Injuries; Magnetic Resonance Imaging; Male; Membrane permeability; Microvasculature; Molecular modelling; Neuroimaging; Neuromodulation; Neuronal Plasticity - physiology; Neurons; Neuropil; Neuroplasticity; Neuroscience; Permeability; Physiology; Proteins; Rats; Scientific equipment and supplies industry; Seizures; Somatosensory cortex; Somatosensory Cortex - physiology; Synaptic plasticity; Transcriptomics; transforming growth factor β; Transforming growth factor-b; Canada; United States; magnetic resonance imaging; blood–brain barrier; caveolae-mediated transcytosis; rat; neuroscience; transforming growth factor β; albumin; synaptic plasticity; human
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.89611

Brain microvessels possess the unique properties of a blood–brain barrier (BBB), tightly regulating the passage of molecules from the blood to the brain neuropil and vice versa. In models of brain injury, BBB dysfunction and the associated leakage of serum albumin to the neuropil have been shown to induce pathological plasticity, neuronal hyper-excitability, and seizures. The effect of neuronal activity on BBB function and whether it plays a role in plasticity in the healthy brain remain unclear. Here 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 β 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.