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Consider how advantageous it might be to have eyes on our hands, rather than on our faces: depth perception would be improved by the greater distance between the eyes, and it would be easy to look into relatively inaccessible spaces by appropriate movement of the hands. The absence of mammals that use this visual strategy draws attention to constraints on how evolution is able to 'design' the nervous system. Energy use in particular, in this case the large amount of energy that would be needed to send visual information along the ∼10 6 optic nerve axons over the length of the arms to the brain (instead of along the much shorter optic nerve), imposes significant design constraints on the nervous system., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In the brain’s gray matter, astrocytes regulate synapse properties, but their role is unclear for the white matter, where myelinated axons rapidly transmit information between gray matter areas. We found that in rodents, neuronal activity raised the intracellular calcium concentration ([Ca 2+ ] i ) in astrocyte processes located near action potential–generating sites in the axon initial segment (AIS) and nodes of Ranvier of myelinated axons. This released adenosine triphosphate, which was converted extracellularly to adenosine and thus, through A 2a receptors, activated HCN2-containing cation channels that regulate two aspects of myelinated axon function: excitability of the AIS and speed of action potential propagation. Variations in astrocyte-derived adenosine level between wake and sleep states or during energy deprivation could thus control white matter information flow and neural circuit function.