New Scholar Award in Aging
Massachusetts Institute of Technology
Role of Neural Progenitors in Adult Hippocampal- and Olfactory Bulb-Dependent Learning and Memory.
Recent studies have demonstrated that neural stem cells exist in the adult nervous system of both lower vertebrates and phylogenetically higher
mammalian organisms, including humans. These findings raise the possibility that new neurons continue to be produced naturally in the adult brain even
after the complete formation of gross neuronal circuits. In the case of amphibians, neural stem cells reside in the peripheral region of the retina and
continue to divide throughout life. In the mammalian central nervous system, two major locations have been defined. One is the subventricular zone
(SVZ), a cell layer lining the wall of the ventricles. The neural stem cells of SVZ of the lateral ventricles migrate via the rostral migratory stream to the
olfactory bulb, where they differentiate into granule cells and periglomerular cells. Another region is the hippocampal dentate gyrus. The neural stem
cells in the subgranular zone of the dentate gyrus continue to divide asymmetrically and differentiate into granule neurons and glial cells. However, the
function of these newly produced neurons in the adult brain remains enigmatic.
The current proposal addresses a fundamental question in neuronal stem cell research: Is adult neurogenesis necessary for function in the adult brain,
especially for learning and memory in animals? For this purpose, we will take an approach that combines genetic manipulation of animals, cell-specific
ablation using immunotoxin, behavioral analyses of hippocampal and olfactory-dependent memories, as well as other technologies. We will develop a
transgenic animal model in which neuronal stem cells can be selectively ablated in a spatiotemporal-specific manner. After ablation, animals will be
tested for various learning and memory tasks to investigate the involvement of generation of new neurons in these processes. Our ultimate goal is to
know whether the generation of new neurons and, hence, the formation of new neuronal circuits, is necessary for learning and memory.