Abstract No.: | B-B2069 |
Country: | Canada |
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Title: | VESICULAR ZINC INFLUENCES PRESYNAPTIC RELEASE AT THE HIPPOCAMPAL MOSSY FIBERS: A ZNT3 KO STUDY |
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Authors/Affiliations: | 1 Nathalie Lavoie*; 1 Katalin Tóth;
1 CRULRG-Université Laval, Québec, QC, Canada
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Content: | The hippocampal mossy fiber axons (MF) arise from the granule cells of the dentate gyrus and provide synaptic input to neurons in the hilus and the CA3 area of the hippocampus. MF synapses have many unique anatomical and physiological properties. The number of active zones and synaptic vesicles that are stored in the presynaptic terminals are several folds higher than in “conventional” synapses and MF inputs show very high degree of short-term facilitation. Another unique feature of this synapse is the unusually high level of chelatable zinc in the synaptic vesicles, which is carried into the vesicles via a specific transporter (ZnT3). It is not currently known why MF terminals contain such a high concentration of zinc and whether there is a correlation between the unique physiological properties of this synapse and their zinc content.
Objectives: We have previously shown that zinc is necessary for the proper function of presynaptic machinery. In this study, we took advantage of the ZnT3 knock-out (KO) mouse to evaluate how the absence of vesicular zinc affects presynaptic release at the mossy fiber terminals.
Methods: We have used wild-type (WT) (ZnT3 +/+) and KO mice (ZnT3 -/-) to perform intracellular patch-clamp recordings as well as extracellular field recordings. MF or associational/collateral (AC) synaptic inputs were evoked with a concentric bipolar tungsten electrode.
Results: Recordings from CA3 pyramidal cells showed a decrease of spontaneous activity (sEPSCs) with the application of membrane-permeable zinc chelators DEDTC in WT but not in KO. Next, we performed several protocols in order to study short-term plasticity. High frequency facilitation from mossy fiber inputs is less efficient in the KO mice or in the WT slices treated with DEDTC. Responses evoked with the stimulation of AC inputs (DCG-IV insensitive) are similar for both WT and KO and show no changes after the application of DETDC.
Conclusion: These data demonstrate that absence of vesicular zinc affects the synaptic machinery implicated in short-term plasticity.
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