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Metabolic Recruitment in Brain Tissue

Journal

ANNUAL REVIEW OF PHYSIOLOGY
Volume 85, Issue -, Pages 115-135

Publisher

ANNUAL REVIEWS
DOI: 10.1146/annurev-physiol-021422-091035

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Information processing in neurons requires significant metabolic resources, but neurons have limited energy stores. Metabolic recruitment is a tissue-level phenomenon where active neurons extract resources from their surroundings. This recruitment involves the release of K+ by neurons, the sensing of K+ by astrocytes, and the switch to a specific metabolic pathway. Glutamate, nitric oxide, and ammonium also act as recruiting signals in different domains.
Information processing imposes urgent metabolic demands on neurons, which have negligible energy stores and restricted access to fuel. Here, we discuss metabolic recruitment, the tissue-level phenomenon whereby active neurons harvest resources from their surroundings. The primary event is the neuronal release of K+ that mirrors workload. Astrocytes sense K+ in exquisite fashion thanks to their unique coexpression of NBCe1 and alpha 2 ss 2 Na+ /K+ ATPase, and within seconds switch to Crabtree metabolism, involving GLUT1, aerobic glycolysis, transient suppression of mitochondrial respiration, and lactate export. The lactate surge serves as a secondary recruiter by inhibiting glucose consumption in distant cells. Additional recruiters are glutamate, nitric oxide, and ammonium, which signal over different spatiotemporal domains. The net outcome of these events is that more glucose, lactate, and oxygen are made available. Metabolic recruitment works alongside neurovascular coupling and various averaging strategies to support the inordinate dynamic range of individual neurons.

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