Hippocampal Neurogenesis in the Aging Brain: The dentate gyrus of the hippocampus is another neurogenic region in the mature brain that continuously produces granule neurons. While the rate of hippocampal neurogenesis is known to decrease with age, it is not known whether newborn neurons in the aged brain differentiate/ mature and integrate into hippocampal circuitry properly. In collaboration with Dr. Cheng (UC Davis), we have investigated the maturation process of mossy fibers of newborn dentate granule neurons. Specifically, we used GIFM to label the NSC-derived newborn neurons in 3, 6, 12, and 18 month old Gli1-CreER/+;Tau-mGFP mice, in which the membrane-bound GFP (mGFP) reporter allows very sensitive detection of mossy fiber projections as they pass through the hilus en route to the CA3 region. Using the serial immune-EM, we are currently characterizing many structural changes associated with aging in development of mossy fiber boutons and their interaction with post-synaptic spines.

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