Place Cells Tell Us about Cognitive Aging

Neurobiological investigations on aging have repeatedly stressed the subtlety and the regional specificity of changes within the hippocampus, affecting synaptic connections, physiology, and plasticity (for review, see Barnes, 1994). These changes may cause subtle shifts in how information is processed by the aging brain. In accordance with this view, age-related changes to hippo-campal place cells are also subtle. Spatial information is certainly reaching and being processed by the aged hippocampus since location-specific activity is equally robust in both young and aged rats. Nevertheless, place cell studies have shown that aged rats have behaviorally significant deficits in encoding and recall of spatial information within the hippocampal region.

In the near future hippocampal place cells may, therefore, serve as a useful tool for investigating three specific aspects of age-related memory impairments. First, it will be important to understand how aged rats fail to encode and recall spatial goals. Researchers have found that weakened processing of external landmarks by place cells during a spatial task predicts performance of the aged rats on that task (Rosenzweig et al.,

2003), and the next step may be to measure the activity of hippocampal cells as the rat is actually learning spatial goals and recalling them.

Second, recent technological advances, such as recordings from twelve independently-movable tetrodes, have made it possible to record cells from several regions of the brain simultaneously. With a better understanding of the particular contributions each region makes to the formation and recall of memories (such as Lee et al.,

2004), the way has recently been paved for information processing studies to match the well-documented subregional specificity of age-related changes to hippcampal neurobiology. These advances may prove important as we aim towards prevention of age-related memory impairments with specifically-targeted pharmacological interventions. Third, place cells of aged rats provide a window for evaluation of these potential drugs. Place cells are already in common use to evaluate effects on memory of receptor-blocking drugs (for example, Kentros et al., 1998) and mutations of specific genes in mice (Cho et al., 1998). With respect to normal aging, therapies that reinstate normal encoding and recall to place cells of aged animals will be particularly promising.

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