Astrocytic glucose metabolism regulates the survival of newborn hippocampal neurons in the adult brain

Abstract

In the adult brain, hippocampal activity precisely regulates the survival of newborn hippocampal neurons. However, the mechanisms by which these neurons acquire metabolites required for survival remain unclear. Using a genetically encoded glucose biosensor and in vivo imaging in freely moving animals, we tracked cellular glucose dynamics during contextual exploration. Newborn neurons recovered intracellular glucose slowly and expressed low levels of glycolysis- and glucose transport-related genes. By contrast, astrocytes surrounding newborn neurons exhibited rapid decreases in intracellular glucose during exploration, followed by prompt recovery afterward. In vivo lactate imaging revealed concurrent increases in astrocytic and extracellular lactate during exploration. Importantly, disrupting astrocytic glucose uptake, lactate production, or lactate transport in astrocytes or newborn neurons impaired activity-dependent survival. These results identify an astrocyte-to-newborn neuron metabolic pathway in which astrocytic glucose metabolism supports newborn neuron survival through lactate, with implications for adult neurogenesis in aging and disease.

Keywords: activity-dependent survival; adult hippocampal neurogenesis; astrocyte-newborn neuron metabolic coupling; glucose metabolism; in vivo biosensor imaging; lactate transport.