366 Nanaline Duke Bldg.
307 Research Dr. Box 3709
Duke University Med. Center
Durham, NC 27710
Email: chay DOT kuo AT duke DOT edu
George W. Brumley Assistant Professor
Cell Biology; Neurobiology; Pediatrics, School of Medicine
We are interested in understanding regenerative capacities in the nervous system, using rodent neurogenesis as a model system. A major part of our current efforts is focused on how to sustain neurogenesis in the adult brain. The answers to this question may be similar to: when do we decide it is time to buy a new computer? Often it is when the hardware can no longer keep up with sophisticated software. Since we are taught that we can’t upgrade our brains (the hardware), how does it keep up as we fill it with new experiences/tasks/skills? Is this accomplished purely by strengthening/weakening/remodeling of existing connections between cells, or could we complement these processes by making and integrating new useful neurons?
We are studying the assembly and function of a neural stem cell niche in the adult rodent brain leading to this possibility. In addition to molecular analyses of lateral ventricular (LV) niche homeostasis under physiological and injury conditions, through a chemical screen we found that cholinergic modulators have robust effects on adult LV neurogenesis ex vivo. In search of potential sources for acetylcholine (ACh) in the LV niche, we uncovered direct cholinergic innervation from previously undescribed subependymal ChAT+ (subep-ChAT+) neurons. These novel cholinergic neurons display morphological and functional differences from neighboring striatal counterparts, and releases ACh into the LV niche in activity-dependent fashion. Our genetic, optogenetic, and electrophysiology experiments showed that subep-ChAT+ neuron activity can directly control adult LV neurogenic proliferation.
Contrary to the view that adult LV neurogenesis is primarily directed by stem-cell intrinsic and local signals, including neurotransmitters acting through bulk-release mechanisms, we have discovered an undescribed gateway connecting neural network activity states to LV NSC proliferation. We are interested in what lies beyond this gateway, and there are many questions to answer going forward, with potentials for modulating neuroregenerative capacities in health and after injury.
Postdoctoral Fellow, HHMI, UCSF, 2002-2007.
M.D., University of Chicago, 2002
Ph.D., University of Chicago, 1997
B.S., Massachusetts Institute of Technology, 1993
Paez-Gonzalez, P., Asrican, B., Rodriguez, E., and Kuo, C.T. 2014. Identification of distinct ChAT+ neurons and activity-dependent control of postnatal SVZ neurogenesis. Nat. Neurosci., doi:10.1038/nn.3734.
Benner, E.J., Luciano, D., Jo, R., Abdi, K., Paez-Gonzalez, P., Sheng, H., Warner, D.S., Liu, C., Eroglu, C., and Kuo, C.T. 2013. Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4. Nature (497): 369-73.
Paez-Gonzalez, P., Abdi, K., Luciano, D., Liu, Y., Soriano-Navarro, M., Rawlins, E., Bennett, V., Garcia-Verdugo, J.M., and Kuo, C.T. 2011. Ank3-dependent SVZ niche assembly is required for the continued production of new neurons. Neuron (71): 61-75.
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