Abstract
BackgroundThe density of functional synapses is an important parameter in determining the efficacy of synaptic transmission. However, how functional presynaptic terminal density is regulated under natural physiological conditions is still poorly understood.ResultsWe studied the factors controlling the density of presynaptic functional terminals at single dendritic branches of hippocampal neurons and found that elevation of intracellular Mg2+ concentration was effective in increasing the density of functional terminals. Interestingly, the upregulation was not due to synaptogenesis, but to the conversion of a considerable proportion of presynaptic terminals from nonfunctional to functional. Mechanistic studies revealed that the nonfunctional terminals had inadequate Ca2+-sensitivity-related proteins, resulting in very low Ca2+ sensitivity within their vesicle release machinery. We identified energy-dependent axonal transport as a primary factor controlling the amount of Ca2+-sensitivity-related proteins in terminals. The elevation of intracellular Mg2+ enhanced local energy supply and promoted the increase of Ca2+-sensitivity-related proteins in terminals, leading to increased functional terminal density.ConclusionsOur study suggests that local energy supply plays a critical role in controlling the density of functional presynaptic terminals, demonstrating the link between energy supply and efficacy of synaptic transmission.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-015-0132-z) contains supplementary material, which is available to authorized users.
Highlights
The density of functional synapses is an important parameter in determining the efficacy of synaptic transmission
Ca2+-sensitivity-related proteins and functional terminal density We investigated whether the increased quantity of Ca2+-sensitivity-related proteins at terminals and subsequently the functionality of terminals as a result of elevated [Mg2+]i was due to enhanced mitochondrial function and local energy supply at dendritic branches
We examined whether the quantity of Ca2+-sensitivity-related proteins or functional terminal density was correlated with mitochondrial density since both are upregulated after the elevation of [Mg2+]i (Figs. 4d, 6b and d)
Summary
The density of functional synapses is an important parameter in determining the efficacy of synaptic transmission. Under physiological conditions, a considerable number of synapses are nonfunctional (i.e. silent/dormant), and the ratio of functional/nonfunctional synapses fluctuates over time. These fluctuations have important implications in brain functions [2], including in neural development [3], physiological function maintenance [4,5,6,7], multiple neural pathologies [8, 5, 9,10,11] and drug addictions [12]. The mechanisms of presynaptic silence are still elusive [16, 17]
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