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26-09-2011 | General practice | Article

Vesicular zinc aids signal transmission in hippocampus


Free abstract

MedWire News: Vesicular zinc is required for signal transmission between neurons, research shows.

"We discovered that zinc is essential to control the efficiency of communication between two critical populations of nerve cells in the hippocampus," said James McNamara (Duke University, Durham, North Carolina, USA), senior investigator of the report.

Publishing the results in the journal Neuron, the group notes that zinc exists in high concentration in the vesicles of excitatory neurons in the mammalian cerebral cortex.

The localization of zinc to the synaptic vesicle suggests it might play a role in communication between nerve cells, say the researchers, but the functional consequences of zinc release have been poorly understood.

In the present study, the group sought to understand the role of zinc in long-term potentiation (LTP), a form of synaptic plasticity believed to be involved in learning and memory. Past studies have attempted to determine if zinc is involved in mossy-form LTP (a form of presynaptic LTP), but the results to date have been contradictory.

To address the issue, the group synthesized a zinc chelator that blocked the effects of synaptically released zinc, while at the same time minimizing the disruption of other pleiotropic intracellular and extracellular functions.

The extracellular zinc chelator, explain the researchers, possesses selective and kinetic properties that allow for the study of transient zinc produced in the synaptic cleft when the mossy fibers are stimulated.

The zinc chelator allowed investigators to compare its effects on the high, but fleeting, concentration of zinc in the synaptic cleft induced by the activation of mossy fibers. The amplitude of the mossy fiber-evoked field excitatory postsynaptic potential was recorded from CA3 pyramidal cell populations.

In the presence of the zinc chelator, increases in the field excitatory postsynaptic potential were attenuated with the induction of high-frequency electrical stimulation. The effects of the zinc chelator were concentration dependent, with inhibition detectable at 50 µM, and similar effects obtained with 100 and 200 µM.

To further study the role of vesicular zinc in the plasticity of the CA3-synapse, the researchers used a mouse model lacking the ZnT3 transporter, which is required for packaging zinc into synaptic vessels.

In these mice, high-frequency electrical stimulation failed to induce a significant induction of paired pulse facilitation, a form of presynaptic plasticity.

The results, according to investigators, show that zinc is required for the induction of presynaptic LTP. Overall, they add that the findings confirm a role for zinc in the regulation of communication, and might be particularly important for the formation of memories and the occurrence of epileptic seizures.

By MedWire Reporters

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