CTBR/Psychology Department Seminar: Modeling Two Aspects of Neuropsychiatric Disorders: Impaired Cognitive Flexibility and Maladaptive Food Intake
Nesha S. Burghardt, PhD
Division of Integrative Neuroscience
Abstract: Exposure to stressful life events is known to impact the onset and course of neuropsychiatric disorders. We are interested in the mechanisms by which stress affects the neural circuits that underlie both the emotional symptoms and cognitive impairments associated with mood and anxiety disorders. Rodent studies have established that chronic exposure to stress leads to multiple changes within the hippocampus, including a decrease in the ability to generate new neurons in adulthood. We investigated a role for adult hippocampal neurogenesis in cognitive flexibility, which is a cognitive function that is impaired in patients with a variety of neuropsychiatric disorders. Using two independent methods of ablating adult neurogenesis and variants of the active place avoidance paradigm to model cognitive flexibility in mice, we found that removal of adult-born cells leads to a specific impairment in the ability to flexibly adapt to a change in contingencies. Our work suggests that medications aimed at upregulating neurogenesis may improve cognitive flexibility in patients, potentially altering the course of their disorder. In a related line of research, we are using a rodent model of anorexia nervosa to investigate how the stress of extreme malnutrition and weight loss during adolescence affects cognitive flexibility and the development of anxiety in adulthood. Activity-based anorexia is a model that involves combining limited access to food with unlimited access to a running wheel. As animals lose weight, they exhibit an increase in running wheel activity, which models excessive exercise reported by the majority of individuals with anorexia nervosa. Although the availability of food is restricted (1-2 hours), mice have the opportunity to consume an unlimited amount of food during that time. Their failure to eat enough to accommodate their increase in energy expenditure leads to significant weight loss, which is comparable to self-starvation exhibited by individuals with anorexia nervosa. Without experimenter intervention, some strains of mice will run themselves to death within a few days. In addition to evaluating the long-term effects of this early life stressor on development, we are testing genetically engineered mice in the activity-based anorexia model to uncover the mechanisms underlying vulnerability to this understudied disorder.
Refreshments will be served!
Supported by the National Institute on Minority Health and Health Disparities, National Institutes of Health - 8 G12 MD007599-27
Psychology Conference Room 612HN
Denise Charles (CTBR) dc674 (at) hunter (dot) cuny (dot) edu