Calcium and metabolic activity in cortical astrocytes during locomotion in mice

The brain active milieu concept holds that the brain function depends on interactions among neurons, glial cells, cells of blood vessels, extracellular space, and extracellular matrix. Within this framework, we investigate the function of astrocytes that form networks and interact with all other elements of the brain active milieu. Astrocytes are not electrically excitable cells but can generate complex spatiotemporal patterns of calcium activity. We investigated different parameters of these patterns recorded in cortical astrocytes with two-photon calcium imaging in awake mice moving on a rotating platform. We also studied calcium activity in hippocampal astrocytes using fibre photometry. In a quiescent state of the animal, calcium activity was characterized by small but regular fluctuations. During running episodes, astrocytic calcium increased significantly in spread and amplitude. Such calcium elevations had a latency from the running onsets and outlasted the running episodes. The functional relevance of delayed and slow calcium transients in the astrocytic network is currently unclear. It could be associated with memory storage or metabolic processes. Therefore, we performed label-free metabolic imaging (Raman microspectrometry) in awake mice running on a treadmill. We observed that running episodes correlate with prolonged increases in the amount of reduced mitochondrial cytochromes in astrocytes but not neurons. On the contrary, the amount of reduced cytochromes in neurons decreased. Our results demonstrate the strong involvement of cortical astrocytes in the brain activity associated with animal behaviour.