Dynamic, experience-dependent modulation of synaptic zinc within the excitatory synapses of the mouse barrel cortex

Increasing evidence suggests that synaptic zinc, found within the axon terminals of a subset of glutamatergic neurons in the cerebral cortex, is intricately involved in cortical plasticity. Using the vibrissae/barrel cortex model of cortical plasticity, we have previously shown manipulations of sensory input leads to rapid changes in synaptic zinc levels within the corresponding regions of the somatotopic map in the cortex. Here, using electron microscopy, we show how some of these changes are mediated at the synaptic level. We found that the density of zincergic synapses increased significantly in layers II/III, IV, and V. In layers IV and V, this change occurred in the absence of a significant increase in excitatory synapse density, which seems to indicate that excitatory synapses, which previously did not contain synaptic zinc, begin to newly house zinc within its synaptic vesicles. Our results show that excitatory neurons can dynamically change the phenotype of the vesicular content of their synapses in response to changes in sensory input. Given the range of modulatory effects zinc can have on neurotransmission, such a change in the complement of vesicular contents presumably allow these neurons to utilize synaptic zinc to facilitate plasticity. Thus, our results further support the role of zinc as an active participant in the processes contributing to experience-dependent cortical plasticity.