Enhanced mitochondrial fusion during a critical period of synaptic plasticity in adult-born neurons

Integration of new neurons into adult hippocampal circuits is a process coordinated by local and long-range synaptic inputs. To achieve stable integration and uniquely contribute to hippocampal function, immature neurons are endowed with a critical period of heightened synaptic plasticity, yet it remains unclear which mechanisms sustain this form of plasticity during neuronal maturation. We found that as new neurons enter their critical period, a transient surge in fusion dynamics stabilizes elongated mitochondrial morphologies in dendrites to fuel synaptic plasticity. Conditional ablation of fusion dynamics to prevent mitochondrial elongation selectively impaired spine plasticity and synaptic potentiation, disrupting neuronal competition for stable circuit integration, ultimately leading to decreased survival. Despite profuse mitochondrial fragmentation, manipulation of competition dynamics was sufficient to restore neuronal survival but left neurons poorly responsive to experience at the circuit level. Thus, by enabling synaptic plasticity during the critical period, mitochondrial fusion facilitates circuit remodeling by adult-born neurons. [Display omitted] •A surge in fusion stabilizes elongated dendritic mitochondria in new neurons•Synaptic plasticity is abrogated in new neurons lacking Mfn1 or Mfn2•Mitochondrial fusion regulates competition dynamics in new neurons•Impaired experience-dependent connectivity rewiring in neurons lacking fusion Circuit integration of adult-born neurons maintains high levels of plasticity in the adult brain. Kochan et al. show that a burst in fusion promotes stable and elongated mitochondrial morphologies along the dendrites of new neurons, fueling experience-dependent synaptic plasticity and competition dynamics within the hippocampal network.