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UBC Theses and Dissertations

Effect of non-invasive neurostimulation on hippocampal plasticity and memory Zhang, Tianrui


Non-invasive stimulation therapies such as electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) are effective therapies for treatment-resistant depression. Although ECT is more efficacious than other treatment options, it is associated with cognitive side effects. By understanding the neurobiological underpinnings of ECT and TMS, we may gain critical insights into both their therapeutic and side effect profiles. In the current project, I used adult hippocampal neurogenesis in mice as a measure of neuroplasticity induced by neurostimulation. First, I directly compared the extent of hippocampal neurogenesis generated acutely by different stimulation modalities, including electroconvulsive shock (ECS), the animal analogue of ECT, and two forms of TMS, the 10Hz repetitive TMS (rTMS) and the intermittent theta burst stimulation (iTBS). I found that ECS increased neurogenesis significantly more than either form of TMS. However, a newer pattern of TMS called intermittent theta burst stimulation (iTBS) showed a greater neurogenic potential than the traditional repetitive TMS (rTMS) when administered acutely and therefore I conducted the first study examining neurogenesis following chronic iTBS. Chronic iTBS application did not affect neurogenesis but altered the new neurons' morphology by increasing the size of pre-synaptic terminals in males. In contrast, chronic ECS induced up to a 2-fold increase in new neuron proliferation and survival, along with an enhancement of dendritic length and pre-synaptic terminal size in both males and females. These findings suggest that the stronger form of stimulation, ECS, is associated with increased neurogenesis, however new neuron addition may not be entirely beneficial. Animals that received chronic ECS were impaired in the performance of an associative memory task. While new neurons support hippocampal functions to improve future cognition, the integration of new neurons may disrupt the existing hippocampal circuit. Although chronic ECS did not decrease the number of developmentally-born neurons, I found that chronic ECS decreased the spine density of developmentally-born neurons in the ventral hippocampus. Overall, this study showed that ECS and TMS had differential effects on adult hippocampal neurogenesis and the ECS-induced neurogenesis may impair cognition by pruning existing synaptic connections.

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