Mitochondrial Delivery Is Essential for Synaptic Potentiation

Abstract

Abstract. Mitochondria, as portable generators that power synaptic function, regulate the ATP supply and calcium homeostasis in the neuron. As molecular interactions within the synapses before and after the potentiation are beginning to be elucidated, the deciding moment during the tetanic stimulation that gives rise to the strengthening of the synapse remains a mystery. Here, I recorded electrically from an intact Drosophila nervous system, while simultaneously using time-lapse confocal microscopy to visualize mitochondria labeled with green fluorescent protein. I show that tetanic stimulation triggers a fast delivery of mitochondria to the synapse, which facilitates synaptic potentiation. Rotenone, an inhibitor of mitochondrial electron transport chain complex I, suppresses mitochondrial transport and abolishes the potentiation of the synapse. Expression of neurofibromin, which improves mitochondrial ATP synthesis in the neuron, enhances the movements of mitochondria to the synapse and promotes post-tetanic potentiation. These findings provide unprecedented evidence that the mitochondrial delivery to the synapse is critical for cellular learning.

Mitochondrial dynamics in neuronal injury, development and plasticity

“…Accordingly, inhibition of mitochondrial ATP production with the complex I inhibitor rotenone interfered with synaptic accumulation of mitochondria and PTP. By contrast, boosting mitochondrial ATP production in motor axons by genetic methods increased PTP (Tong, 2007). Further illustrating the importance of synaptic localization of mitochondria in short-term synaptic plasticity, Drp1 loss-of-function mutations in Drosophila depleted mitochondria from motor nerve terminals and inhibited mobilization of the reserve pool of synaptic vesicles (Verstreken et al, 2005) (Fig.…”

“…At the Drosophila neuromuscular junction (NMJ), synaptic potentiation induced by tetanic stimulation, i.e. post-tetanic potentiation (PTP) of motor nerves increases transport of mitochondria to synaptic terminals (Tong, 2007). Accordingly, inhibition of mitochondrial ATP production with the complex I inhibitor rotenone interfered with synaptic accumulation of mitochondria and PTP.…”

Neurologic Dysfunction and Male Infertility in Drosophila porin Mutants

“…DRP1, dynamin-related protein, is a GTPase that is a central component of the mitochondrial outer membrane fission machinery involved in regulating mitochondrial dynamics (60). It was also recently reported that pharmacological inhibition of complex I activity in Drosophila larvae significantly reduces presynaptic anterograde trafficking of mitochondria (61). Mitochondria isolated from porin-deficient flies demonstrate a significant reduction in complex I activity (Fig.…”

Inhibitory Effects of Quercetin on Muscle-type of Nicotinic Acetylcholine Receptor-Mediated Ion Currents Expressed in Xenopus Oocytes

“…Thus, since muscle-type nicotinic acetylcholine receptors play an important role for skeletal and respiration-related muscle contraction and relaxation, these receptors are one of main targets of drugs and toxins. In previous reports, flavonoids derived from plants or tea extracts were demonstrated to affect acetylcholine release, muscle contraction and neuromuscular junction activity [14][15][16][17][18]. However, relatively little is known how flavonoids including quercetin regulate muscle-type nicotinic acetylcholine receptor channel activity.…”

“…1). Flavonoids derived from plants or tea extracts affect acetylcholine release, muscle contraction or neuromuscular junction activity [14][15][16][17][18]. Especially, quercetin inhibits end-plate currents at the mouse neuromuscular junction [19].…”