Unknown

Dataset Information

0

Mossy fiber Zn2+ spillover modulates heterosynaptic N-methyl-D-aspartate receptor activity in hippocampal CA3 circuits.


ABSTRACT: Although Zn2+ is contained in large amounts in the synaptic terminals of hippocampal mossy fibers (MFs), its physiological role in synaptic transmission is poorly understood. By using the newly developed high-sensitivity Zn2+ indicator ZnAF-2, the spatiotemporal dynamics of Zn2+ was monitored in rat hippocampal slices. When high-frequency stimulation was delivered to the MFs, the concentration of extracellular Zn2+ was immediately elevated in the stratum lucidum, followed by a mild increase in the stratum radiatum adjacent to the stratum lucidum, but not in the distal area of stratum radiatum. The Zn2+ increase was insensitive to a non-N-methyl-d-aspartate (NMDA) receptor antagonist but was efficiently attenuated by tetrodotoxin or Ca2+-free medium, suggesting that Zn2+ is released by MF synaptic terminals in an activity-dependent manner, and thereafter diffuses extracellularly into the neighboring stratum radiatum. Electrophysiological analyses revealed that NMDA receptor-mediated synaptic responses in CA3 proximal stratum radiatum were inhibited in the immediate aftermath of MF activation and that this inhibition was no longer observed in the presence of a Zn2+-chelating agent. Thus, Zn2+ serves as a spatiotemporal mediator in imprinting the history of MF activity in contiguous hippocampal networks. We predict herein a novel form of metaplasticity, i.e., an experience-dependent non-Hebbian modulation of synaptic plasticity.

SUBMITTER: Ueno S 

PROVIDER: S-EPMC2173116 | biostudies-other | 2002 Jul

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC2660276 | biostudies-literature
| S-EPMC3545206 | biostudies-literature
| S-EPMC6927957 | biostudies-literature
| S-EPMC4020060 | biostudies-literature
| S-EPMC6351853 | biostudies-literature
| S-EPMC3964078 | biostudies-literature
| S-EPMC10942602 | biostudies-literature
| S-EPMC3055459 | biostudies-literature
| S-EPMC8058084 | biostudies-literature
| S-EPMC2854556 | biostudies-literature