Experience-dependent persistent expression of zif268 during rest is preserved in the aged dentate gyrus.

BACKGROUND: Aging is typically accompanied by memory decline and changes in hippocampal function. Among these changes is a decline in the activity of the dentate gyrus (DG) during behavior. Lasting memory, however, is thought to also require recapitulation of recent memory traces during subsequent rest - a phenomenon, termed memory trace reactivation, which is compromised in hippocampal CA1 with progressive age. This process has yet to be assessed in the aged DG, despite its prominent role in age-related memory impairment. Using zif268 transcription to measure granule cell recruitment, DG activity in adult and aged animals was assessed both during spatial exploration and as animals remained at rest in the home cage in order to detect potential memory-related replay. RESULTS: Consistent with the observation of memory trace reactivation in DG, the probability that an individual granule cell transcribes zif268 during rest in the animal's home cage is increased by recent experience in a novel environment. Surprisingly, a comparable increase was observed in the probability of granule cells in the aged DG expressing zif268 during rest. Moreover, no significant age-related difference was observed in the number of granule cells expressing zif268 during rest. Thus, the number and pattern of granule cell expression of zif268 during rest is preserved in aged animals, despite a significant decline in exploration-related zif268 expression. CONCLUSIONS: These data lead to the hypothesis that the input the aged DG receives from backprojections from CA3 (the region widely hypothesized to mediate reactivation) remains functionally intact despite loss of innervation from the perforant path.

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.