Journal
NEURON
Volume 108, Issue 5, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2020.09.002
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Funding
- UCSD Graduate Training Program in Cellular and Molecular Pharmacology through an institutional training grant from the National Institute of General Medical Sciences [T32 GM007752]
- NIH/NINDS [R01 NS091281]
- Rita Allen Foundation
- Klingenstein-Simons Fellowship Awards in Neuroscience
- CureAlz Fund
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The blood vessels in the central nervous system (CNS) have a series of unique properties, termed the blood brain barrier (BBB), which stringently regulate the entry of molecules into the brain, thus maintaining proper brain homeostasis. We sought to understand whether neuronal activity could regulate BBB properties. Using both chemogenetics and a volitional behavior paradigm, we identified a core set of brain endothelial genes whose expression is regulated by neuronal activity. In particular, neuronal activity regulates BBB efflux transporter expression and function, which is critical for excluding many small lipophilic molecules from the brain parenchyma. Furthermore, we found that neuronal activity regulates the expression of circadian clock genes within brain endothelial cells, which in turn mediate the activity-dependent control of BBB efflux transport. These results have important clinical implications for CNS drug delivery and clearance of CNS waste products, including Ab, and for understanding how neuronal activity can modulate diurnal processes.
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