Axonal Connection, Hippocampus, and Aging
We are interested in axon guidance, a research field that deals with everything about how the neuronal network in our brain is built and refined during early development, and how this network matures and changes throughout the entire lifetime. In adult mammalian brain, the subgranular zone of the hippocampal dentate gyrus retains the capacity for neurogenesis throughout life. These adult-born neurons are functionally integrated into the existing hippocampal circuitry, where they are involved in learning and memory. Disruptions to such adult hippocampal neurogenesis (AHN) are implicated in human neurological disorders, including Alzheimer’s disease, depression, epilepsy, and age-related cognitive decline.
Our objective is to understand why AHN becomes less efficient with age and how aging process changes the new axonal connections in adult hippocampus. Like their mature counterparts, newborn dentate granule cells (GCs) in the adult brain receive synaptic inputs from the perforant pathway and send axonal projections along the mossy fiber pathway into stratum lucidum of the CA3 subfield. In CA3, the newborn mossy fiber boutons (MFBs) establish synaptic contacts with large spiny structures termed thorny excrescences at the proximal dendrites of mature CA3 pyramidal cells. We and others have shown that it takes about eight weeks for newborn GCs in young adult mouse hippocampus to form mature MFB contacts with CA3 pyramidal cells. Adult-born MFBs establish novel synaptic contacts in two main patterns: 1) de novo synaptogenesis and 2) replacement of preexisting contacts through a progressive encroachment on postsynaptic territory. The mechanisms underlying such development are unknown.
We combine mouse genetics, confocal and electron microscopic imaging, and array tomography-based molecular phenotyping to delineate how newborn GCs change with age and to elucidate the underlying mechanisms that control the generation and synaptic integration of newborn GCs in aged mice.
- PDF, 1997-2002, University of California San Francisco Stanford University, USA
- Ph.D., 1995, Harvard University, USA
- MD, 1989, College of Medicine, National Taiwan University
- NACADA Region 9 Excellence in Advising Award (2016)
- UC Davis Academic Advising Award (2015)
- Faculty Service Award, Neuroscience Graduate Group, UC Davis (2012)
- Klingenstein Fellowship Award (2004)
- Alfred P. Sloan Research Fellow (2004)
- Whitehall Foundation Grant Award (2003)
- Howard Hughes Medical Institute Physician Postdoctoral Fellowship(1997-2002)
- Pharmacia Biotech & Science Prize for Young Scientists in Molecular Biology, Regional winner from North America (1996)
- Liu, W.-W., Chen, S.-Y., Cheng, C.-H., Cheng, H.-J., Huang, P.-H. (2014) Blm-s, a BH3-only protein enriched in postmitotic immature neurons, is transcriptionally upregulated by p53 during DNA damage. Cell Reports 9: 166-179.
- Failor, S., Chapman, B., Cheng, H.-J. (2015) Retinal waves regulate afferent terminal targeting in the early visual pathway. Proc. Natl. Acad. Sci. USA 112: E2957-E2966.
- Davis, Z. W., Chapman, B., Cheng, H.-J. (2015) Increasing spontaneous retinal activity before eye opening accelerates the development of geniculate receptive fields. J. Neurosci. 35:14612-14623.
- Chen, S.-Y., Ho, C.-T., Liu, W.-W., Lucanic, M., Shih, H.- M., Huang, P.-H., Cheng, H.-J. (2018) Regulation of axon repulsion by MAX-1 SUMOylation and AP-3. Proc. Natl. Acad. Sci. USA 115: E8236-E8245.
- Murray, K. D., Liu, X.-B., King, A. N., Luu, J., Cheng, H.-J. (2020) Age-related changes in synaptic plasticity associated with mossy fiber terminal integration during adult neurogenesis. eNeuro 7(3): ENEURO.0030-20.
