Somatic mosaic approaches and the aging brain.

ABSTRACT

Elucidating the function of neural pathways in the aging mammalian brain is a formidable task. Mechanisms that underlie aging and pathogenesis in specific brain circuits have been particularly elusive. However, animal models have been exploited in studies related to normative and pathogenic aging. Traditional transgenic animals represent permanent germ-line alterations in gene expression; changes that are present during development, remain indefinitely and likely invoke compensatory changes in the animal. In contrast, conditional transgenic animals combined with somatic gene delivery afford precise temporal and spatial gene regulation. In this review, we will detail current somatic mosaic approaches to study networks involved in the recognition, interpretation and recall of spatial representations, the septohippocampal pathway. We will also highlight potential uses for this approach in Alzheimer's disease, a complex pathophysiological state involving changes in many cellular pathways.