Li et al. used time-lapse microscopy to visualize fluorescently labeled mitochondria in cultured rat hippocampal neurons and observed that, whereas most dendritic mitochondria were localized in the dendrite shaft, the fraction in protrusions (spines and filopodia) was affected by developmental stage, increasing during periods of synaptogenesis and spine formation. Repeated depolarization through exposure to 90 mM KCl stimulated the formation of new protrusions and of synapses (evaluated by staining for PSD-95) and increased both the fraction of mitochondria in protrusions and the percentage of protrusions containing mitochondria. Similarly, localized high-frequency synaptic stimuli elicited a localized increase in the size of dendritic spines followed by an increase in the percentage of spines with mitochondria. Overexpression of Drp-1 (dynamin-related protein-1, a guanosine triphosphatase involved in regulating mitochondrial fission) increased dendritic mitochondrial density, as well as the density of dendritic spines and synapses, whereas overexpression of a dominant-negative form of Drp-1 depleted dendrites of mitochondria and reduced the density of dendritic spines and synapses. Creatine, which stimulates mitochondrial respiration, also increased synaptic density. Moreover, both Drp-1 and creatine enhanced synaptogenesis in response to repeated depolarization with 90 mM KCl. Finally, depolarization with 50 mM KCl reduced the rate of mitochondrial movement and promoted fission over fusion, whereas tetrodotoxin had the opposite effects. Thus, the activity and dendritic distribution of mitochondria appear to play a role in regulating synaptic density and activity-dependent synaptogenesis, whereas neuronal activity appears to affect the motility, overall morphology, and distribution of mitochondria. Schuman and Chan provide context in a Preview.
Z. Li, K.-I. Okamoto, Y. Hayashi, M. Sheng, The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119, 873-887 (2004). [Online Journal]
E. Schuman, D. Chan, Fueling synapses. Cell 119, 738-740 (2004). [Online Journal]