A.J. Robison, PhD
Assistant Professor, Physiology
Ph.D., 2005, Vanderbilt University
Drug addiction exacts an enormous medical, financial, and emotional toll on society in the form of overdose and health complications, family disintegration, loss of employment, and crime. Although most individuals are exposed to drugs of abuse, only a subset become addicted, and the molecular and physiological mechanisms that determine this addiction process remain incompletely defined. Similarly, though many people may be exposed to extreme stressors, like war, starvation, or chronic abuse, some individuals experience post-traumatic stress disorder and/or major depressive disorder, while others appear resilient. What are the molecular and physiological processes that underlie these opposing adaptations?
Research in the Robison Lab focuses on how models of drug addiction and chronic stress alter gene expression in discreet brain regions, particularly the hippocampus. The hippocampus is a part of the limbic system long associated with consolidation of memories in humans and in rodent models of spatial learning. We also know that the hippocampus plays a major role in craving and seeking of drugs of abuse, as well as in the manifestation of multiple symptoms of major depressive disorder. Some of our questions include:
- How is the transcriptional and epigenetic machinery of the hippocampus altered by drugs or stress?
- How do drugs and stress affect hippocampal neurons, particularly at the synapse?
- Can manipulation of gene structure and transcription in the hippocampus affect responses to drugs or stress?
We use transgenic mice and viral gene-transfer tools to manipulate hippocampal expression of specific genes, as well as the machinery that regulates chromatin structure and gene transcription. We then examine the effects of these manipulations at multiple levels:
- Biochemistry- Western blotting, immunohistochemistry, and proteomics to quantify protein expression and localization
- Behavior- mouse models of drug response and PTSD/depression
- Physiology- field and whole-cell recording of neurons in mouse brain slices to monitor functional changes in synaptic activity
- Structure- confocal and electron microscopy to examine dendritic arborization and spine morphology
- Molecular Biology- quantitative PCR, chromatin immunoprecipitation, and next generation deep sequencing to quantify RNA levels and changes in DNA structure and transcription factor binding
While we mainly utilize rodent models, we also collaborate with other labs to acquire post-mortem brain samples from human addiction and depression patients. Thus, by combining various cutting-edge techniques across multiple systems, we hope to uncover potential targets for therapeutic intervention in human drug addiction and mood disorders.