| Neocortical circuits are persistently required to change in order to adjust and adapt to the demands of the external environment. Increasing evidence indicates that vesicular zinc is an important component of this process, acting to mediate and modulate cortical plasticity.;The relationship between vesicular zinc in the barrel cortex and biochemical processes was examined by comparing protein and gene expression in barrel cortices derived from a transgenic mouse that does not express vesicular zinc (ZnT3 KO mouse) with control animals. Additionally, by examining barrel cortices that had been deprived of sensory input, differences in the biochemical characteristics of experience-dependent plasticity arising from the absence of vesicular zinc were also evaluated. Using these techniques, several proteins and genes involved in neurotransmission and synaptic plasticity were found to be differentially expressed between control and ZnT3 KO barrel cortices both basally and with cortical plasticity.;Given that the gene that encodes for metallothionein 3 (MT3), a zinc homeostasis protein, was less expressed in ZnT3 KO barrel cortices, the experience-dependent regulation of vesicular zinc was investigated in male and female MT3 KO mice. Compared to controls, MT3 KO mice, regardless of sex, were found to have a greater zincergic response to whisker plucking through their lifespan.;Together, these data indicate that the experience-dependent regulation of vesicular zinc is an active process that is intricately entwined with biochemical factors involved in neurotransmission and synaptic plasticity.;The goal of this thesis was to further elucidate the characteristics of the experience-dependent regulation of vesicular zinc in the mammalian cortex, using the mouse barrel cortex as a model system with which to generate cortical plasticity. Ultrastructural analysis revealed that the increase in vesicular zinc staining that occurs within sensory deprived barrels following whisker plucking is at least partially mediated by an augmentation in the number of synapses containing vesicular zinc. This increase was observed in LII/III-V and, in the case of LIV and V, occurred in the absence of a concurrent increase in the number of excitatory synapses, indicating that pre-existing synapses likely changed their “phenotype” and began to newly house zinc within their vesicles. |
