This study investigates the activity-dependent compartmentalization of dendritic mitochondria morphology in CA1 pyramidal neurons (PNs) of the hippocampus. Mitochondria in these neurons exhibit a significant degree of subcellular and layer-specific compartmentalization, with mitochondria in the apical tuft being highly fused and elongated, while those in the basal and apical oblique dendrites are more fragmented. The molecular mechanisms underlying this compartmentalization are not well understood. The study demonstrates that this compartment-specific morphology requires activity-dependent, Ca²⁺- and Camkk2-dependent activation of AMPK, which phosphorylates two key effectors: Mff, a pro-fission Drp1 receptor, and Mtfri1, an anti-fusion protein. These findings uncover a signaling pathway that regulates mitochondrial morphology in a spatially precise and activity-dependent manner, contributing to the functional specialization of neuronal compartments. The results also highlight the importance of Ca²⁺ dynamics and neuronal activity in shaping mitochondrial morphology, with lower Ca²⁺ levels leading to fusion-dominant mitochondrial elongation in the apical tuft, and higher Ca²⁺ levels promoting fission-dominant morphology in more proximal dendritic compartments.This study investigates the activity-dependent compartmentalization of dendritic mitochondria morphology in CA1 pyramidal neurons (PNs) of the hippocampus. Mitochondria in these neurons exhibit a significant degree of subcellular and layer-specific compartmentalization, with mitochondria in the apical tuft being highly fused and elongated, while those in the basal and apical oblique dendrites are more fragmented. The molecular mechanisms underlying this compartmentalization are not well understood. The study demonstrates that this compartment-specific morphology requires activity-dependent, Ca²⁺- and Camkk2-dependent activation of AMPK, which phosphorylates two key effectors: Mff, a pro-fission Drp1 receptor, and Mtfri1, an anti-fusion protein. These findings uncover a signaling pathway that regulates mitochondrial morphology in a spatially precise and activity-dependent manner, contributing to the functional specialization of neuronal compartments. The results also highlight the importance of Ca²⁺ dynamics and neuronal activity in shaping mitochondrial morphology, with lower Ca²⁺ levels leading to fusion-dominant mitochondrial elongation in the apical tuft, and higher Ca²⁺ levels promoting fission-dominant morphology in more proximal dendritic compartments.