Chapters authored
Computer Simulations of Hippocampal Mossy Fiber Cleft Zinc Movements
Zinc ions have key regulatory, structural, and catalytic functions and mediate a variety of intra- and intercellular processes. The hippocampal mossy fiber boutons contain large amounts of free or loosely bound vesicular zinc, which can be co-released with glutamate. Zinc can interact with a variety of ionic channels (N-VDCCs, L-VDCCs, KATP), glutamate receptors (AMPA, KA, NMDA 2A, 2B), glutamate transporters (GLAST, EAAT4), and molecules (ATP). The dynamic properties of cleft free, complexed, and total zinc were addressed, considering the known concentration and affinity of various cleft zinc sensitive sites, mainly in the postsynaptic area and in glial cells. The computer model included three different zinc release processes, with short, medium, and long duration, described, like the uptake ones, by alpha functions. The results suggest that, depending on the amount of release, zinc clearance is largely due, either, to zinc binding to NMDA 2A receptor sites or to glial GLAST transporters.
Part of the book: Advances in Neural Signal Processing
FAD-Linked Autofluorescence and Chemically-Evoked Zinc Changes at Hippocampal Mossy Fiber-CA3 Synapses
Glutamatergic vesicles in hippocampal mossy fiber presynaptic boutons release zinc, which plays a modulatory role in synaptic activity and LTP. In this work, a fluorescence microscopy technique and the fluorescent probe for cytosolic zinc, Newport Green (NG), were applied, in a combined study of autofluorescence and zinc changes at the hippocampal mossy fiber-CA3 synaptic system. In particular, the dynamics of flavoprotein (FAD) autofluorescence signals, was compared to that of postsynaptic zinc signals, elicited both by high K+ (20 mM) and by tetraethylammonium (TEA, 25 mM). The real zinc signals were obtained subtracting autofluorescence values, from corresponding total NG-fluorescence data. Both autofluorescence and zinc-related fluorescence were raised by high K+. In contrast, the same signals were reduced during TEA exposure. It is suggested that the initial outburst of TEA-evoked zinc release might activate ATP-sensitive K+ (KATP) channels, as part of a safeguard mechanism against excessive glutamatergic action. This would cause sustained inhibition of zinc signals and a more reduced mitochondrial state. In favor of the “KATP channel hypothesis”, the KATP channel blocker tolbutamide (250 μM) nearly suppressed the TEA-evoked fluorescence changes. It is concluded that recording autofluorescence from brain slices is essential for the accurate assessment of zinc signals and actions.
Part of the book: Hippocampus