Integrated Calendar

The etiology of schizophrenia is complex and largely unknown, but consistent findings report a strong genetic component. While several potential schizophrenia-susceptibility genes have been identified, effect sizes are very small and replication is inconsistent, likely because of the complexity of human polymorphisms, genetic and clinical heterogeneity and the potential uncontrollable impact of gene-gene and gene-environment interactions. In this context, mutant mice bearing targeted mutations of schizophrenia-susceptibility genes are unique tools to elucidate the neurobiological basis of this devastating disorder.
Using COMT*dysbindin-1 double mutant mice, we investigated the COMT*dysbindin-1 gene-gene interacting effects in the expression of rodents’ correlates of schizophrenia-relevant behavioral abnormalities. A major focus of our work is centered on how to dissect higher order cognitive functions in mice with high translational validity to human studies.
In particular, in contrast to single genetic modifications, the combined decreased activity of both COMT and dysbindin-1 produced marked working memory, recency memory and attentional set-shifting deficits, and amphetamine supersensitivity; all abnormalities ascribed as mice’ correlates of schizophrenia-like symptoms. Based on this, we found evidence of the same non-linear genetic interaction in prefrontal cortical function in humans. Finally, to disentangle how COMT*dysbindin-1 interaction might converge in dopaminergic signaling, we measured in these double mutant mice dopamine levels in the PFC and dorsal striatum by in vivo microdialysis. Interestingly, concomitant COMT*dysbindin-1 reduction diminished dopamine levels in PFC and striatum, while amphetamine-evoked dopamine increase was attenuated in the PFC but exacerbated in the striatum. These findings illustrate a clinically relevant experimental animal model based on a predicted epistatic interaction of two schizophrenia-susceptibility genes and unravel interesting genetic mechanisms in the etiology of this mental illness.

Time-urgent policy decisions are increasingly benefiting from the scientific assessments of risks and outcomes. However the ability to inject science into decision processes can be haphazard, requiring awareness of potential tools and involvement in the policy decisions. I hope to provide some insight on how science is drawn into decisions through a series of examples including the Fukushima Daiichi accident and aircraft safety to the Gulf oil spill and Ebola.

In fMRI studies, contrast-to-noise ratio and spatial resolution can be improved by using ultra-high magnetic fields. Traditionally, fMRI experiments are performed using the Blood Oxygen Level Dependent (BOLD) technique based on echo planar imaging (EPI) acquisition strategies. When using EPI, certain unwanted effects such as image blurring, distortions and signal voids enhance as the magnetic field strength increases. In the first part of my talk I will present the use of a different acquisition scheme, spatiotemporal encoding (SPEN), which has the potential to improve image quality, offering an attractive alternative to EPI for UHF fMRI.
In the second part of my presentation I will focus on two other approaches to imaging brain function: Diffusion fMRI (DfMRI) and Manganese Enhanced MRI (MEMRI). Specifically, I will present studies which highlight the advantages and disadvantages of each of these techniques with respect to BOLD.