Mechanisms of perisynaptic astrocyte depolarization in response to neuronal activity

Recent studies show that astrocytic depolarization can be induced at the periphery of cortical somatosensory astrocytes, proposed to be the contact sites between neurons and astrocytes. However, specific mechanisms causing astrocytic depolarization have yet to be confirmed due to limitations in experimental techniques. Here, we constructed a computational whole-cell astrocyte model to assess which channels were responsible for astrocyte depolarization. Our simulations show that, unlike depolarization by bath application of potassium, local depolarization by potassium uptake and glutamate transporters required very large spillover and high-frequency stimulation. On the contrary, the model reproduced experimentally observed depolarizations by activating N-methyl-d-aspartate receptor (NMDAR) or -aminobutyric acid A receptor (GABAAR), on the astrocyte. Our models suggest two mechanisms for astrocyte depolarization, either by neurotransmitters or by potassium and glutamate transporters, which substantially alters the spatio-temporal dynamics of the phenomenon. These insights suggest new mechanisms of how astrocytic processes can locally regulate learning and memory.