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Elisa Dumett, Ph.D., Winner of the 2018 NIMH Three-Minute Talks Competition

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The study of hippocampal function is important for understanding the basic processes of memory encoding and how they are altered in psychiatric illness. A way that we can look more closely at the role of the hippocampus and memory is by using ephemera-based functional coupling of the hippocampus to the rest of the brain during encoding. This shows us the brain regions that are activated or deactivated in parallel to the hippocampus. It is also interesting to look at how brain function is influenced by environmental and genetic factors. Importantly, gene environment interactions helped to better model systems under some genetic control, like hippocampal function.

Therefore, I chose to look a hippocampal functional coupling through the lens of environmental factor of urbanicity and the genetic factor BDNF. Life in cities carries both positives, like better quality of life and decreased infant mortality rate, as well as negatives, like increased risk of cardiovascular or psychiatric illnesses. Urbanicity quantifies the extent of urban exposure during childhood based on the relative population size people are raised in. Brain-derived neurotropic factor, or BDNF is critical for hippocampal function. There is allelic variation in the BDNF gene that swaps a methionine for a valine. As seen here and these cultured hippocampal neurons, the Val BDNF genotype is trafficked well across the cell and into its dendrites, unlike the Met BDNF genotype.

People with even one copy of the Met allele display poor hippocampal mediated memory performance. I chose a visual memory encoding task known to activate the hippocampus to identify any urbanicity by the BDNF genotype interactions. Because of the difference in health outcomes for people from urban environments and the differences in synaptic and cellular function for the Met BDNF enough genotype, I predicted that urban Met BDNF genotype individuals might be distinct from other groups. I found two brain regions that displayed a significant interaction between urbanicity and BDNF genotype on right hippocampal functional coupling. The first region was the inferential parietal labial, known to be involved in episodic memory encoding. Urban Met carriers showed reduced hippocampal functional coupling opposite to that found in rural met carriers.

The second region we found to show a significant interaction was a lateral geniculate nucleus, a region of the thalamus involved in vision. The interaction in this region followed a different pattern, although, still highlighting a difference between urban and rural groups. Among urban reared subjects, Met carriers showed increased coupling, whereas no difference was found among rural-reared subjects. The fact that these two interactions followed different patterns reinforces the idea that the environmental factor of urbanicity can alter the coupling relationships across BDNF genotypes. Ultimately, this study provides a template for exploring the effects of gene environment interactions for general brain function and how this might be altered in psychiatric illness.