Defined motoneurons in the brain stem & spinal cord are damaged during human ALS & corresponding mouse models of this disease. The selective vulnerability of motoneurons has been linked to a specialized calcium handling and an exceptional sensitivity to mitochondrial disturbances. To study underlying events, we investigated the postnatal development of calcium homeostasis in vulnerable facial motoneurons (FMNs) by performing simultaneous patch clamp & Ca2+ measurements in mouse brain stem slices. After postnatal day 4(P4), FMNs had rapid decay phases of voltage induced Ca2+ transients ([tau]= 0.43s) and calcium buffering capacities of 46. Moreover, mitochondrial disruption after bath application of the uncoupler FCCP provoked a retardation of (Ca2+)i clearance rates and substantial Ca2+ release from mitochondrial stores at P4. In younger animals (P0), FMNs displayed significantly slower decay times of Ca2+ transients ([tau]=1.85s) and large buffering capacities of 134. also (Ca2+)i clearance rates were only mildly affected after mitochondrial disruption. These observations suggest that selectively vulnerable MNs reorganise their (Ca2+)i homeostasis during the first days of development. In particular, FMNs significantly accelerate their Ca2+ decay time constants between P0 and P4 as a result of both a 3-fold reduction in Ca2+ buffering capacity and an enhanced role of mitochondrial Ca2+ uptake.