Neurons require a constant supply of energy to function, some of which is supplied by astrocytes in the form of lactate. In a recent study published in Nature, Theparambil et al. explored how astrocytes can synchronize lactate release with the energy needs of neurons. To start, the authors showed that electrical stimulation of rat hippocampal slices evokes astrocytic glucose metabolism (marked by cAMP–PKA signaling) and lactate release. Neuronal activity is associated with the release of purines such as adenosine, and treatment of brain slices with adenosine was also sufficient to stimulate astrocytic glucose metabolism. Inhibition of the adenosine A2B receptor in astrocytes blocked the effect of electrical stimulation or adenosine treatment on astrocyte cAMP–PKA activity and lactate release. Mice with astrocyte-specific depletion of the A2B receptor also experienced deficits in long-term potentiation, object recognition and sleep–wake regulation. Together, these results suggest that the adenosine signaling through the A2B receptor enables astrocytes to detect and support neuronal energy needs, which has implications for normal brain function and cognition.

Original reference: Nature https://doi.org/10.1038/s41586-024-07611-w (2024)