Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Neuroscience

Supervisor

Bussey, Timothy J.

2nd Supervisor

Saksida, Lisa M.

Joint Supervisor

Abstract

The variability in the symptomatology of depressive disorders and antidepressant treatment response has led to an increased interest in the molecular, cellular, and circuit mechanisms of many aspects of affect. Evidence suggests a reduction in adult hippocampal neurogenesis (AHN) is associated with an increase in depression-like behaviour, though much of this evidence has been from studies using aversive tests (e.g., forced swim test). Here, I used touchscreen operant chambers, which allow for non-aversive and translational testing, to test the hypothesis that AHN plays a contributing role in emotion regulation. A panel of three touchscreen tests were chosen to assess different aspects of depression-relevant reward-related behaviour, namely probabilistic reversal learning, progressive ratio, and extinction learning. Results across these tests largely indicate that AHN knockdown does not affect sensitivity to feedback information, motivation across a variety of reward strengths, and the ability to cease responding after reward withdrawal. Therefore, it seems that a role of AHN in emotion regulation may only apply in stressful, but not non-aversive, conditions.

Summary for Lay Audience

Depressive and other mood disorders are major causes of illness and impair well-being worldwide. Despite the high occurrence of these disorders, their complexity makes determining appropriate treatment difficult as their underlying causes are largely unknown. There has been mounting evidence to suggest that the generation of new neurons (known as neurogenesis) in the hippocampus, a brain area commonly associated with learning and memory, might be involved in depressive and other mood disorders. Particularly, people with depression, and animal models of depression, often have fewer newborn neurons in this brain area and antidepressant treatment has often been found to increase the amount of neurogenesis. However, a lot of this evidence comes from animal studies using stressful methods. For my thesis, I wanted to determine if neurogenesis impacts depression-related behaviour in non-stressful situations. Considering one major characteristic of depression in humans is impaired reward responding, I used rodent touchscreen behavioural systems to test whether mice with reduced neurogenesis had changes in their responses to reward. I chose three tests, each assessing different aspects of reward-related behaviours. These aspects were (1) whether the outcome of a response would impact later responses (for example, whether getting rewarded for a response would increase the likelihood that the same response would be repeated), (2) willingness to exert effort to receive a reward, or motivation, and (3) whether responding would stop once the reward was removed. For all three tests, I did not find strong evidence for a role of decreased neurogenesis in changing reward-related behaviours, meaning that decreasing neurogenesis does not impact depression-relevant behaviours in non-stressful conditions. These results point to the importance of stress in producing depression-relevant behaviours in mice. A popular theory for the cause of depression in humans is that there is some underlying biological cause that must be combined with an external trigger for the disorder to occur — such an underlying cause may be reduced neurogenesis and such a trigger may be stress. My thesis project shows that reducing neurogenesis, by itself, does not impact depression-relevant reward-related behaviour when stress is not involved.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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