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Use of Synaptic Zinc Histochemistry to Reveal Different Regions and Laminae in the Developing and Adult Brain
Published on: October 29, 2017
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Modelling zinc changes at the hippocampal mossy fiber synaptic cleft.
M E Quinta-Ferreira1,2, F D S Sampaio Dos Aidos3,4,5, C M Matias3,6
1CNC- Center for Neuroscience and Cell Biology, University of Coimbra, P-3004-504, Coimbra, Portugal. emilia@uc.pt.
Journal of Computational Neuroscience
|October 4, 2016
Summary
This study models synaptic zinc dynamics, revealing that glutamate transporters (GLAST) are key for clearing high zinc concentrations, while NMDA receptors also contribute to clearing lower zinc levels in the hippocampus.
Area of Science:
- Neuroscience
- Computational Biology
- Biochemistry
Background:
- Zinc is a transition metal found in high concentrations in hippocampal mossy fibers, co-released with glutamate.
- Synaptic zinc has a neuromodulatory role, influenced by release dynamics and binding kinetics.
- Understanding zinc's synaptic action requires quantifying concentration changes and binding interactions.
Purpose of the Study:
- To model total, free, and complexed zinc concentrations in a synaptic cleft after evoked release.
- To estimate the time course and magnitude of zinc complex concentrations.
- To elucidate the roles of different binding sites in synaptic zinc clearance.
Main Methods:
- Developed a computational model simulating zinc release and uptake dynamics in the synaptic cleft.
- Assumed zinc and glutamate co-release with similar temporal profiles.
- Incorporated binding kinetics to NMDA receptors, GLAST transporters, AMPA receptors, and other molecules.
Main Results:
- At low zinc release levels, NMDA receptors and GLAST transporters are primary clearance mechanisms.
- At high zinc release levels, GLAST transporters dominate zinc binding, forming complexes an order of magnitude higher than with NMDA sites.
- Binding to AMPA receptors, KATP channels, and ATP molecules contributes minimally to synaptic zinc clearance.
Conclusions:
- Synaptic zinc clearance mechanisms vary significantly with the amount of zinc released.
- GLAST transporters play a crucial role in clearing substantial amounts of synaptic zinc.
- The model provides insights into the spatiotemporal dynamics of zinc in the synaptic environment.
