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      Extremely Low Frequency Electromagnetic Fields Facilitate Vesicle Endocytosis by Increasing Presynaptic Calcium Channel Expression at a Central Synapse

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          Abstract

          Accumulating evidence suggests significant biological effects caused by extremely low frequency electromagnetic fields (ELF-EMF). Although exo-endocytosis plays crucial physical and biological roles in neuronal communication, studies on how ELF-EMF regulates this process are scarce. By directly measuring calcium currents and membrane capacitance at a large mammalian central nervous synapse, the calyx of Held, we report for the first time that ELF-EMF critically affects synaptic transmission and plasticity. Exposure to ELF-EMF for 8 to 10 days dramatically increases the calcium influx upon stimulation and facilitates all forms of vesicle endocytosis, including slow and rapid endocytosis, endocytosis overshoot and bulk endocytosis, but does not affect the RRP size and exocytosis. Exposure to ELF-EMF also potentiates PTP, a form of short-term plasticity, increasing its peak amplitude without impacting its time course. We further investigated the underlying mechanisms and found that calcium channel expression, including the P/Q, N, and R subtypes, at the presynaptic nerve terminal was enhanced, accounting for the increased calcium influx upon stimulation. Thus, we conclude that exposure to ELF-EMF facilitates vesicle endocytosis and synaptic plasticity in a calcium-dependent manner by increasing calcium channel expression at the nerve terminal.

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          Synaptic computation.

          Neurons are often considered to be the computational engines of the brain, with synapses acting solely as conveyers of information. But the diverse types of synaptic plasticity and the range of timescales over which they operate suggest that synapses have a more active role in information processing. Long-term changes in the transmission properties of synapses provide a physiological substrate for learning and memory, whereas short-term changes support a variety of computations. By expressing several forms of synaptic plasticity, a single neuron can convey an array of different signals to the neural circuit in which it operates.
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            Synaptic vesicle pools.

            Communication between cells reaches its highest degree of specialization at chemical synapses. Some synapses talk in a 'whisper'; others 'shout'. The 'louder' the synapse, the more synaptic vesicles are needed to maintain effective transmission, ranging from a few hundred (whisperers) to nearly a million (shouters). These vesicles reside in different 'pools', which have been given a bewildering array of names. In this review, we focus on five tissue preparations in which synaptic vesicle pools have been identified and thoroughly characterized. We argue that, in each preparation, each vesicle can be assigned to one of three distinct pools.
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              Short-term presynaptic plasticity.

              Different types of synapses are specialized to interpret spike trains in their own way by virtue of the complement of short-term synaptic plasticity mechanisms they possess. Numerous types of short-term, use-dependent synaptic plasticity regulate neurotransmitter release. Short-term depression is prominent after a single conditioning stimulus and recovers in seconds. Sustained presynaptic activation can result in more profound depression that recovers more slowly. An enhancement of release known as facilitation is prominent after single conditioning stimuli and lasts for hundreds of milliseconds. Finally, tetanic activation can enhance synaptic strength for tens of seconds to minutes through processes known as augmentation and posttetantic potentiation. Progress in clarifying the properties, mechanisms, and functional roles of these forms of short-term plasticity is reviewed here.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                18 February 2016
                2016
                : 6
                : 21774
                Affiliations
                [1 ]State Key Laboratory of Medical Neurobiology, Department of Physiology and Biophysics, School of Life Sciences and Collaborative Innovation Centre for Brain Science, Fudan University , Shanghai, 200438, P.R.China
                [2 ]Institute of Genetics, State Key Laboratory of Genetic Engineering, Fudan University , Shanghai, 200433, P.R.China
                [3 ]Institutes of Brain Science, School of Life Sciences and State Key Laboratory of Medical Neurobiology, Fudan University , Shanghai, 200438, P.R.China
                [4 ]Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University , Shanghai, 200080, P.R.China
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                srep21774
                10.1038/srep21774
                4757866
                26887777
                46fd836c-fe2f-434d-af22-dcb9e1a4d37e
                Copyright © 2016, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 27 September 2015
                : 01 February 2016
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