In this Review, the authors have explored the most recent data regarding how microglia are directly involved in the neuronal circuit’s formation related to cognition and energy metabolism. Excessive microglial activation due to environmental factors, such as overconsumption of saturated fats from the diet and senescence can trigger not only an inflammatory response but also the disturbance in neuronal survival-related functions, resulting in altered regulation of energy balance and lastly in cognitive decline. The authors also highlighted the importance of the maintenance of homeostatic microglial-neuronal crosstalk for the proper development and preservation of hippocampal and hypothalamic neuronal networks.