Department of Brain and Cognitive Sciences, The School of Brain Sciences and Cognition, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Uri Monsonego
Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Lynn T Yang
Department of Integrative Biology, University of California, Berkeley, Berkeley, United States; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States
Lior Schori
Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Lyna Kamintsky
Department of Medical Neuroscience, Dalhousie University, Halifax, Canada
Sheida Mirloo
Department of Medical Neuroscience, Dalhousie University, Halifax, Canada
Itamar Burger
Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Sarit Uzzan
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Rishi Patel
Department of Integrative Biology, University of California, Berkeley, Berkeley, United States
Department of Integrative Biology, University of California, Berkeley, Berkeley, United States
Ofer Prager
Department of Brain and Cognitive Sciences, The School of Brain Sciences and Cognition, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Department of Integrative Biology, University of California, Berkeley, Berkeley, United States; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States
Department of Brain and Cognitive Sciences, The School of Brain Sciences and Cognition, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Department of Medical Neuroscience, Dalhousie University, Halifax, Canada
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.
