Genes, Brain, and Behavior under Stress

Organizer: BJ Casey, Sacker Institute, Weill Medical College of Cornell

Adaptation to changing environments requires neuronal plasticity, or refinement of neural pathways with new experiences. Difficulty in adjusting to new environments and recognition of safe environments has been suggested to lie at the core of many affective disorders (Castrén, 2005; Charney and Manji, 2004; Duman et al., 1997; Nestler et al., 2002). This flexibility in adjusting to changing environments is altered by experiential events. Stress in adult experimental animals reduces volume and production of new neurons in the hippocampus and enhanced dendritic arborization of the amygdala, two regions shown to be important in learning about the environment and safety of that environment. Brain-derived neurotrophic factor (BDNF), an important mediator of neuronal plasticity in the developing and adult brain (Barde et al., 1987; Leibrock et al., 1989; Thoenen, 1995; Lu, 2003) and thought to be essential in learning, is reduced with stress (Smith et al., 1995). These findings suggest that stress can have a significant impact on important neurotrophic factors essential for development, learning and neuronal plasticity. Moreover, disruption in these processes may lead to atypical cognitive and social functioning that may predispose individuals to psychiatric disorders of anxiety and depression.

4:00 pm - 6:00 pm: Presentations

Francis Lee, Weill Medical College of Cornell, "Brain-Derived Neurotrophin Factor (BDNF) Transgenic Mouse Model."

Kevin Bath, The Rockefeller University and Weill Medical College of Cornell, "Anxiety-Related Behaviors in the BDNF Mouse Model."

Conor Liston, The Rockefeller University and Weill Medical College of Cornell, "Animal and Human Imaging Studies of Stress."

Barbara Ganzel, Cornell University-Ithaca and Weill Medical College of Cornell University, "Imaging Studies of 911: Neural Correlates of Trauma."

Nim Tottenham, Weill Medical College of Cornell, "Stress and the Developing Human: Impact of Orphanges on Development."

Kevin Bath, "Anxiety-Related Behaviors in the BDNF Mouse Model."
Postdoctoral Fellow, Weill Medical College of Cornell and Rockefeller University. Brain-derived neurotrophic factor (BDNF) is a member of the broader neurotrophin family of proteins. BDNF is critical for the early development and maintained plasticity of the brain. Recently, a naturally occurring mutation in the human BDNF gene has been discovered, resulting in a valine to methionine substitution (val66met) in the prodomain of the protein. This single nucleotide polymorphism (SNP) has been associated with numerous psychiatric disorders in humans. We have generated a knock-in mouse model of this SNP, and shown that mice carrying the Met mutation have similar Hp memory impairments to those shown previously in humans. We also have shown that mouse carriers of the Met allele have an additional phenotype in displaying elevated levels of anxiety-related behaviors.

Barbara Ganzel, "Imaging Studies of 911: Neural Correlates of Trauma."
More than half of the population experiences trauma in their lifetime and trauma exposure is a strong predictor of later mental disorder. Sensitization of the amygdala has been suggested as a mechanism underlying this association but there has been little evidence for this in people without posttraumatic stress disorder (PTSD). Twenty-two healthy adults were scanned with functional magnetic resonance imaging while they passively viewed emotional faces. Eleven (5 female) were near the World Trade Center (WTC) on 9/11/01 and 11 (5 female) lived more than 200 miles away. Lifetime trauma exposure and behavioral measures were also assessed.

Bilateral amygdala activity in the fear-calm contrast was significantl