Browsing by Author "Thackray, Sarah Elizabeth"

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    Anatomy and Function of Synaptic Zinc in the Striatum
    (2015-09-28) Thackray, Sarah Elizabeth; Dyck, Richard
    Synaptic zinc is located in many regions of the brain. One area that contains a high amount is the input center of the basal ganglia: the striatum. Environmental enrichment was used to examine potential changes in morphology of striatal cells of mice with (ZnT3 wildtype) and without (ZnT3 knockout) the zinc transporter (ZnT3) necessary to load zinc into vesicles. No changes were found in dendritic length for any regions of the striatum. However, all regions of the striatum showed an increase in spine density in both genotypes, with enriched ZnT3 KO mice having a greater increase in the nucleus accumbens region. ZnT3 mice were also tested on a battery of motor behavioural tasks. ZnT3 KO mice may be hyperactive, as evidenced by their performance on the pole task, and impulsive, as evidenced by their inaccurate performance on a skilled reach task, when compared to ZnT3 WT mice.
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    The Role of Vesicular Zinc in Instrumental Conditioning and Drug-Evoked Plasticity
    (2020-09-03) Thackray, Sarah Elizabeth; Dyck, Richard H.; Antle, Michael C.; Sargin, Derya; Borgland, Stephanie Laureen; Tzounopoulos, Thanos
    Zinc is critical for the functioning of all cells. A subset of the zinc in the brain (vesicular zinc) acts as a neurotransmitter and is capable of modulating a variety of receptors. Not all areas of the brain contain vesicular zinc; however, there are high amounts found in the striatum, neocortex, and limbic regions. Some regions have received more attention than others concerning the function of vesicular zinc. Those that have been studied have found that vesicular zinc is important for synaptic plasticity. Less studied regions include areas involved in instrumental conditioning, motivation and reward. A commonly used model to study the role of vesicular zinc is the zinc transporter 3 (ZnT3) knockout (KO) mouse which lack the protein solely responsible for loading zinc into vesicles and thus shows a complete absence of vesicular zinc. The purpose of this thesis was to examine the behaviour of ZnT3 KO mice (compared to wildtype mice) on instrumental conditioning tasks as well as on their response to cocaine. Drugs of abuse, including cocaine, can be used to probe the functioning of the reward pathways. Results found no difference in instrumental conditioning in ZnT3 KO mice. There were, however, differences in response to cocaine which, for the most part, were restricted to one sex or the other. In general, ZnT3 KO mice had reduced locomotor response to cocaine, particularly at higher doses and in females. They also showed differences in “memory” of cocaine experience, with male KO mice more affected. Overall, findings suggest that vesicular zinc is involved in both acute response to cocaine and in the long-term memory of drug-associated cues.