Increased pattern separation in the aged fascia dentata.

One prominent impairment associated with aging is a deficit in the ability of the hippocampus to form stable contextual representations. Place-specific firing in granule cells of the fascia dentata (FD) is thought to aid the formation of multiple stable memory representations by disambiguating similar experiences (a process termed pattern separation), such as when an animal repeatedly enters similar environments or contexts. Using zif268/egr1 as a marker of cellular activity, we show that aged animals, which have altered place maps in other areas of the hippocampal formation, also show altered granule cell activity during multiple visits to similar environments. That is, the FD of aged animals is more likely to recruit distinct granule cell populations, and thus show greater pattern separation, during two visits to similar (or even the same) environments. However, if two highly distinct environments are visited, this age-related increase in pattern separation is no longer apparent. Moreover, increased pattern separation in similar environments correlates with decline in the ability of aged animals to disambiguate similar contexts in a sequential spatial recognition task.