ASSESSING GENE, ENVIRONMENT, AND GENE × ENVIRONMENT EFFECTS ON ANXIETY-RELATED AND LEARNING BEHAVIORS IN MOUSE MODELS

Open Access
Author:
Bressler, Amanda Jean
Graduate Program:
Chemistry
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
August 05, 2011
Committee Members:
  • Anne Milasincic Andrews, Dissertation Advisor
  • Anne Milasincic Andrews, Committee Chair
  • Christine Dolan Keating, Committee Chair
  • Andrew Ewing, Committee Member
  • Byron C Jones, Committee Member
  • David John Vandenbergh, Committee Member
Keywords:
  • learning
  • brain-derived neurotrophic factor
  • serotonin transporter
  • anxiety
  • mouse model
  • stress
Abstract:
The pathological mechanisms underlying human psychiatric disorders, including anxiety and mood disorders, are far from understood. Mouse models of aspects of anxiety-related disorders are tools for investigating key aspects of anxiety related to complex human behaviors. By characterizing behavioral phenotypes in these mouse models, we can begin to understand how genetic and environmental factors interact to increase susceptibility of developing anxiety and depression. The principle focus of this research was to investigate how altered serotonin and brain-derived neurotrophic factor (BDNF) systems, alone and in combination with environmental factors including chronic stress and aging, influence behavior. Mice with constitutive reductions in serotonin transporter (SERT) or BDNF expression were studied to identify changes in anxiety-related behavior. Because anxiety and mood are known to influence learning and memory, the latter were also investigated. Mice treated with a serotonergic neurotoxin were studied to characterize the phenotypic consequences of depleting brain serotonin levels in adulthood. A secondary focus of this research was to devise a battery of behavioral tests to probe a wide range of different aspects of anxiety-related behaviors. Two strains of recombinant inbred mice were compared. Overall, the findings begin to elucidate how genetic, environmental, and gene × environment-induced changes in mouse anxiety and learning behaviors can be used to understand the complex interactions of factors modulating human anxiety-related disorders.