Synaptic Vesicle Exocytosis in Hippocampal Synaptosomes Correlates Directly with Total Mitochondrial Volume

Abstract

Synaptic plasticity in many regions of the central nervous system leads to the continuous adjustment of synaptic strength, which is essential for learning and memory. In this study, we show by visualizing synaptic vesicle release in mouse hippocampal synaptosomes that presynaptic mitochondria and specifically, their capacities for ATP production are essential determinants of synaptic vesicle exocytosis and its magnitude. Total internal reflection microscopy of FM1-43 loaded hippocampal synaptosomes showed that inhibition of mitochondrial oxidative phosphorylation reduces evoked synaptic release. This reduction was accompanied by a substantial drop in synaptosomal ATP levels. However, cytosolic calcium influx was not affected. Structural characterization of stimulated hippocampal synaptosomes revealed that higher total presynaptic mitochondrial volumes were consistently associated with higher levels of exocytosis. Thus, synaptic vesicle release is linked to the presynaptic ability to regenerate ATP, which itself is a utility of mitochondrial density and activity.

Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen–glucose deprivation

“…Increased expression of GAD has been considered as a sign of GABAergic hyperactivity (Li et al, 2010). GADmediated GABA-synthesis is activated early after OGD and accompanied by enhanced mitochondria activity and synaptic GABA-release (Madl and Royer, 2000;Schwartz-Bloom and Sah, 2001;Jin et al, 2003;Ivannikov et al, 2013). These processes provide extracellular GABA-accumulation that, depending on ischemia conditions, contributes either to protection, as it was in our experiments in OGD-conditions, or to death of the pyramidal neurons.…”

Brain-derived Neurotrophic Factor (BDNF)-induced Mitochondrial Motility Arrest and Presynaptic Docking Contribute to BDNF-enhanced Synaptic Transmission

“…It has also been reported that BDNFenhanced neurotransmitter release is due to increases in the number of vesicles docked at the active zone of individual synapses (50), which is partly dependent on mitochondrial ATP production (51). One recent study has shown that presynaptic mitochondria are essential determinants of synaptic vesicle exocytosis, primarily via ATP synthesis (52). In the case of BDNF-enhanced neurotransmitter release, although an overall increase in ATP production was not observed (Fig.…”

Presynaptic mitochondrial morphology in monkey prefrontal cortex correlates with working memory and is improved with estrogen treatment

“…Mitochondria are very dynamic organelles that perform various metabolic functions, including energy production and facilitation of synaptic transmission (22,23). In neurons, mitochondria are trafficked throughout the dendritic and axonal extents and are more stationary at synaptic sites, where energy demand is especially high (24, 25).…”