Experience-dependent regulation of synaptic zinc is impaired in the cortex of aged mice

Abstract

Zinc plays an important role in synaptic signaling in the mammalian cerebral cortex. Zinc is sequestered into presynaptic vesicles of subpopulations of glutamatergic neurons and is released by depolarization, in a calcium-dependent manner. As the majority of mechanisms that have been suggested to participate in experience-dependent alterations in synaptic strength in the cerebral cortex implicate signaling by glutamate, it stands to reason that zincergic signaling might also be crucial. Here we show that synaptic zinc is rapidly and dynamically modulated in relation to alterations in sensory input and that this response is highly age-dependent. Juvenile, adult, and aged mice were subjected to whisker removal and levels of staining for synaptic zinc in deprived and non-deprived cortical barrels were quantitatively assessed at post-deprivation times ranging from 3 h to 21 days. In the first 12 h, zinc levels increased slightly, but significantly, in all groups. At later time points, zinc levels increased robustly (23%) in the youngest group by 24 h and remained elevated through 7 days. By contrast, deprivation-induced changes in zinc staining in aged animals, achieved their maximal levels at 12 h (approximately 10%) and steadily declined thereafter. Adult animals revealed a biphasic, intermediate change with time. In all age groups, levels of zinc staining returned to baseline by 21 days after whisker plucking. However, only in juvenile and adult mice did we observe that the level of zinc staining in deprived barrel hollows, was correlated with the length of whiskers as they regrew. Our data suggest that alterations in the regulation of synaptic zinc may be involved with decrements of synaptic plasticity that accompany senescence.