| Abstract No.: | 204 |
| Country: | Canada |
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| Title: | INTRAVESICULAR ZINC AND THE MOSSY FIBER SYNAPSE |
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| Authors/Affiliations: | 1 Katalin Toth*;
1 Centre de recherche Universite Laval, Quebec, 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. Granule cells are the first step in the coding process that will lead to memory formation in the hippocampus. MF synapses have many unique anatomical and physiological properties. These unique properties play a crucial role in how information is ‘translated’ by the granule cells. 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. Currently it is not known why MF terminals contain such high concentration of zinc, and whether there is a correlation between the unique physiological properties of this synapse and their zinc content.
We have used membrane-permeable (DEDTC) and membrane-impermeable (CaEDTA) zinc chelators to differentiate between the effect of synaptically released and vesicle-bound zinc. Recordings from CA3 pyramidal cells showed a decrease of spontaneous activity (sEPSCs) with the application of DEDTC, while CaEDTA had no effect. Recordings from CA1 pyramidal cells showed no change in activity which demonstrates that DEDTC effect is specific to CA3 terminals. However, same manipulation had virtually no effect in the presence of TTX (mEPSCs). This result could be explained by a cellular mechanism which is only activated at higher level of activity. In order to test this hypothesis, we have studied the effect of Brefeldin A (BFA), a selective blocker of the AP3-dependent vesicle recycling pathway. BFA-treatment (10µg/ml) selectively decreased the frequency of sEPSCs with higher then 100 pA amplitude, while sEPSCs with smaller amplitude were unaffected. It has been shown that zinc transport into vesicles (via specific transporter ZnT-3) seems to be related to the AP3 pathway. Therefore, we investigated whether the previously described effect of zinc chelation is still present in BFA-treated slices. Our data show that DEDTC does not change the frequency of sEPSCs in the presence of BFA. This suggests that the zinc-dependent presynaptic machinery and AP3-dependent endocytosis are overlapping intracellular pathways. These changes in the ability of the presynaptic terminal to effectively recycle synaptic vesicles lead to reduction in paired-pulse and frequency facilitation of the mossy fiber events.
Our data indicte the vesicular zinc is important for the proper recycling of synaptic vesicles after increased presynaptic activity.
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