Stress Neurobiology and Neurogenetics: Bridging the Genotype-Phenotype Gap

The biological response to stressors is concerned with the maintenance of homeostasis in the presence of real or perceived challenges. This process requires numerous adaptive responses involving changes in the central nervous and neuroendocrine systems. When a situation is perceived as stressful, the brain activates many neuronal circuits, linking centers involved in sensory, motor, autonomic, neuroendocrine, cognitive, and emotional functions in order to adapt to the demand. However, the details of the pathways by which the brain translates stressful stimuli into the final, integrated biological response are presently poorly understood. Nevertheless, it is clear that dysregulation of these responses to stressors can have severe psychological and physiological consequences. There is much evidence suggesting that inappropriate regulation, disproportional intensity, or chronic and/or irreversible activation of the stress response is linked to the etiology and pathophysiology of anxiety disorders and depression.

Understanding the neurobiology of stress by centering on the specific genes and brain circuits, which are associated with, or altered by, the stress response, will provide important insights into the brain mechanisms by which stress affects psychological and physiological disorders. Our Department focuses on integrated multidisciplinary projects from gene to behavior using state-of-the-art mouse genetics and animal models. We employ integrated molecular, biochemical, pharmacological, physiological and behavioral methods, converging on the generation of genetic mouse models as an in vivo tool, in order to study the central pathways and molecular mechanisms mediating the organism's stress response. Defining the contributions of known and novel gene products to the maintenance of stress-linked homeostasis may improve our ability to design therapeutic interventions for, and thus manage, stress-related psychiatric disorders.

The collective long-term goal of our department's research is to elucidate the pathways and mechanisms by which stressors are perceived, processed, and transduced into neuroendocrine and behavioral responses under healthy and pathological conditions. Our current projects include the following interlinked topics:

• Stress response regulation and circuitry (J. Deussing, M. Schmidt, C. Wotjak)
• Etiology and pathophysiology of stress-induced psychopathologies (J. Deussing, M. Schmidt, C. Wotjak)
• Genetic risk factors and their interaction with the environment (J. Deussing, M. Schmidt, M. Schröder)
• MicroRNAs and epigenetic regulation of the stress response (J. Deussing)
• Early life stress reprogramming (O. Almeida, M. Schmidt, M. Schröder)
• Stress and metabolic functions (O. Almeida, M. Schmidt, M. Schröder)
• Endophenotypes and group social interaction (C. Wotjak)
• Stress vulnerability and resilience (J. Deussing, M. Schmidt, M. Schröder, C. Wotjak)
• Stress, cognition and neuronal plasticity (O. Almeida, A. Attardo, M. Schmidt, C. Wotjak)