Abstract :
An increasing body of evidence suggests that astrocytes participate in higher-brain functions, controlling from synaptic transmission to global brain waves and learning and memory processes. Different mechanisms have been proposed to mediate these astrocyte-dependent processes, astrocytic lactate release and calcium-dependent gliotransmission being the main known effectors. The existence of control of brain functions by astrocytes suggests that astrocytes may shape brain functions in response to experience as much as neurons, thus constituting the phenomenon of astrocyte plasticity. In neurons, the transcription factor CREB is the best known coordinator of synaptic and intrinsic plasticity. The fact that, in astrocytes, CREB activation is also activity-dependent, positions CREB as an ideal target to promote plasticity-related changes in astrocytes, too. In this study, we have analyzed the effect of the activation of CREB-dependent transcription in astrocytes, specifically regarding calcium signals and metabolism. We have demonstrated that activation of CREB-dependent transcription reduces cytosolic calcium events via mitochondria and increases lactate release, which may have impact on synaptic transmission. An important contribution of the study is the molecular analysis of astrocytic mitochondria, which has revealed that astrocytes may use fuels other than glucose such as fatty acids to meet basic energy metabolic demands. Taken together, our results establish astrocytic CREB as a hub in astrocyte-plasticity and shed light on the interplay between plasticity and energy metabolism in