| Neurons have a polarized structure that physically separates distinct physiological and biochemical mechanisms into individual cellular compartments. While structurally the soma, dendrites, spines, and the axon with the axon terminal are physically separate, they intercommunicate in two distinct ways. First, slow communication via intracellular trafficking is essential for the mediation of long-term changes in neuronal electrical properties. Second, fast communication via action potential propagation and intrinsic membrane potential oscillations are critical to the incoming signal transformation. Both of these mechanisms are supported by the specialized structures in the cytosol and sub-plasmalemmal compartments that rely on distinct energy sources.;Here we present a comprehensive study of energy pathways in neuronal compartments. We imaged calcium transients in cultured cerebellar granule cells and Purkinje cells in acute slices. We found that the soma, dendrites, and spines share similar energy generating mechanisms, and that impairment of glycolysis considerably increases calcium clearance time. Furthermore, the observed clearance delay in the spines was ∼ 20% larger than in the dendrite. Taken together, this indicates that calcium clearance mechanisms in the plasma membrane of the soma, dendrites, and spines is modulated by glycolysis, with the spines relying exclusively on glycolysis due to the lack of mitochondria from their structure. Surprisingly, inhibition of mitochondria had no immediate effects on calcium kinetics. In contrast to the soma, the major ATP consumer in the presynaptic terminal is synaptic vesicle release machinery rather than ionic clearance. This shift in ATP consumption is accompanied by a change in ATP production. Indeed, we show that mitochondria are the chief source of ATP at the axon terminal. Mitochondrial depolarization in cerebellar and hippocampal synaptosomes led to a 60% drop in ATP, and abolition of synaptic release. Moreover, structural analysis of synaptosomes revealed a relationship between mitochondria and synaptic activity. Indeed, synaptosomal mitochondrial numbers were positively correlated with the number clathrin-coated vesicles, suggesting a link between mitochondria, ATP, and endocytosis.;In conclusion, this study provides robust evidence in support of the compartmental neuron model. Functional specialization of neuronal compartments results in distinct energy demands satisfied by the redistribution and specialization of energy pathways. |
