Deeper understanding of how transcription is regulated by chromatin modification dynamics is going to be central in choosing targets for Metformin mouse therapeutic optimization of cognition during aging. When the activity of ensembles of hippocampal cells are examined in behaving young and old rats, interesting changes are observed in cell population dynamics between spatial experiences. O’Keefe & Dostrovsky (1971) first described the activity patterns of individual hippocampal cells as place-specific, and named these cells ‘place cells’. As discussed earlier, this was a prime impetus behind the development of the idea that the hippocampus had an important role in cognitive mapping and

in spatial strategies that drive behavioral performance. selleck screening library All three principal hippocampal cell types show place-related firing, although only CA1 and CA3 pyramidal cells have been recorded and compared across age groups. While there is stability of CA1 and CA3 spatial firing patterns within a given recording session for young and old rats (i.e., the distribution of cell firing in the

first half of the behavior session is highly correlated with the distribution of place-specific firing in the second half of the session), between-session dynamics are different between age groups and across cell types. For CA1, the cell firing pattern, or ‘map’, is stable in young rats across two Montelukast Sodium daily sessions in an identical environment. For old rats, however, the cell firing pattern can completely change from one session to the next, and occurs on about a third of the recording days for any individual old rat. In other words, the hippocampus ‘remaps’ as though

the first and second session are recorded in different environments (Barnes et al., 1997). For CA3, on the other hand, when environments are changed between sessions, young rats remap appropriately between the first and second sessions. For old rats, however, the hippocampus appears to sometimes retrieve the same map for the two distinct environments. In this case, the hippocampus fails to remap (Wilson et al., 2005). It is likely that these altered dynamics of hippocampal representation of space contribute to the spatial behavioral differences noted between age groups. In the context of changing circuit dynamics with age, it is important to highlight conditions under which the hippocampus is activated differentially in young and older adults in fMRI experiments. One among a number of examples of this is a study by Maguire & Frith (2003) who used fMRI imaging methods that assessed hippocampal and medial prefrontal cortical network activation in young and older adults. While in the scanner, the participants retrieved details of specific episodic memories for autobiographical events.