The long-term goal of our project is to map neural circuits in order to understand how adult neurogenesis-induced neural circuits account for cognition and mental stability, and how dysfunctions of the same neural circuits underlie neurological, affective, addictive and psychiatric diseases. The persistent production and incorporation of new granule cells into the hippocampal circuitry (neurogenesis) has been implicated in the hippocampal function and dysfunction. However, it remains enigmatic how homogeneous neuronal population of newly generated GCs can play such a diverse role that is phenotypically and mechanistically different from each other. We hypothesize that the function of newly generated granule cells is specified by neural circuits in which new granule cells are making connections with distinct brain input neurons, and that different disorders disrupt sub-regions of neural circuits that new granule cells are involvedin. Using kainic acid (KA)-induced epileptogenic mouse model, we will test this hypothesis by mapping neural circuits of adult-born new granule cells in the normal and epileptogenic mice. To directly address this issue, we have recently developed a rabies virus-mediated retrograde tracing system that allows us to trace the neurons presynaptic to new granule cells in the adult mouse hippocampus. Using this unique retrograde tracing method, we will map the normal and aberrant epileptogenic neural circuits of new granule cells.
Vivar, C., Potter, M. C., Choi, J., Lee, J., Stringer, T. P., Callaway, E. M., Gage, F. H., Suh, H*., van Praag, H*. (2012) Monosynaptic inputs to new neurons in the dentate gyrus.Nature Communications3, Article number: 1107 (* co-corresponding authors)
Zhu, Q., Pao G., Huynh A., Chou SJ, Suh, H., Tonnu N., O’Leary D., Gage, F, H., Verma, I, M. (2011) BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nature 477, 179-84.
Suh, H., Deng, W., Gage F, H. (2009) Signaling in Adult Neurogenesis. Annual Review Cell and Developmental Biology 25, 253-75.
Suh, H., Consiglio A., Ray J., Sawai T., D’Amour K., Gage, F, H. (2007) In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus. Cell Stem Cell1, 515-528.
Lerner Research Institute
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Cleveland, Ohio 44195