Active presynaptic ribosomes in the mammalian brain, and altered transmitter release after protein synthesis inhibition
Abstract
Presynaptic neuronal activity requires the localization of thousands of proteins that are typically synthesized in the soma and transported to nerve terminals. Local translation for some dendritic proteins occurs, but local translation in mammalian presynaptic nerve terminals is difficult to demonstrate. Here, we show an essential ribosomal component, 5.8S rRNA, at a glutamatergic nerve terminal in the mammalian brain. We also show active translation in nerve terminals, in situ, in brain slices demonstrating ongoing presynaptic protein synthesis in the mammalian brain. Shortly after inhibiting translation, the presynaptic terminal exhibits increased spontaneous release, an increased paired pulse ratio, an increased vesicle replenishment rate during stimulation trains, and a reduced initial probability of release. The rise and decay rates of postsynaptic responses were not affected. We conclude that ongoing protein synthesis can limit excessive vesicle release which reduces the vesicle replenishment rate, thus conserving the energy required for maintaining synaptic transmission.
Data availability
All data analysed during this study are included in the manuscript and supporting files. Source data values and images have been provided for Figure 1 and 2. All measured data is provided for Figures 3, 4, 5, 6, and 7, with individual measurement (including ~15,000 measurements for Fig 6).
Article and author information
Author details
Funding
National Institutes of Health (NS051401-42)
- Kenneth G Paradiso
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Every effort was made to minimize suffering. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#10-062) of Rutgers University.
Copyright
© 2018, Scarnati et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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