Laminar variation in neuronal viability and trophic dependence in neocortical slices

Organotypic slices are used frequently in studies of central nervous system development and function because they provide excellent experimental acces s with significant preservation of cellular context and relationships. With in a slice, however, a variety of factors may cause individual classes of n eurons to respond differently to the culture environment. Differences in de afferentation, cellular maturation, trophic dependence and ongoing naturall y occurring cell death may produce changes in the neuronal population that are transparent to the experimenter but that could affect experimental resu lts significantly. In this study, we examined the distribution and prevalen ce of cell death among neurons in each cortical layer in organotypic slices . In addition, we assessed the ability of several neurotrophic factors to a meliorate neuronal death in each cortical layer. Within the first 24 hr in culture, there was striking laminar variation in the extent of neuronal dea th in culture, which could not be accounted for by the pattern of programme d cell death in vivo. In addition, neurons in the six layers of the neocort ex differed in the degree to which they could be rescued by neurotrophic fa ctors. These data suggest that differential neuronal death and rescue are i mportant considerations in studies utilizing organotypic slices and may rep resent particularly confounding variables in studies of effects of trophic factors in such preparations. (C) 2001 Wiley-Liss, Inc.