Investigations of the neurobiological sequelae of aging have led to an increasingly sophisticated understanding of the extent and specificity of age-related changes in neuronal connectivity and cellular physiology. How these changes mediate alterations in behavior remain less well understood. In part, this is true because of the difficulties in bridging the gaps between behavioral, network and cellular levels of analysis. Dramatic advances have been made in recent years in the theory of how information may be represented, stored and retrieved in neural networks, and in the methodology for studying interactions among groups of neurons. Neurons in the hippocampus, for example, convey sufficient information within a given behavioral context about an animal's location in space, to enable the position of an animal to be derived from the firing pattern of 50 or more simultaneously recorded cells. The hippocampal firing pattern for a given environment is map-like in a formal sense, but questions remain about whether and how the rest of the brain makes use of these 'maps', and the extent to which the neurobiological changes known to occur during aging impact the dynamics of these network properties. A number of recent experiments have begun to examine these issues. For example, in young rats, the map for a given environment is usually stable from one experience to another, but can exhibit dramatic rearrangements when the sensory or behavioral context changes (remapping). For old rats, remapping can occur with no change in external stimuli, but, paradoxically, maps can remain stable under conditions of dramatic change in sensory context. This suggests that the old hippocampus can fail to retrieve consistent maps, and can also fail to generate new maps appropriately. In young rats, there is a rapid increase in the spatial information content of the map with experience, as predicted by theories of sequence learning, and this phenomenon is NMDA receptor-dependent. This effect is much less robust in old rats, suggesting a failure of encoding mechanisms at the biophysical level (such as associative storage mechanisms and synaptic connectivity). The experiments outlined in this proposal are designed with three goals in mind: 1) to clarify the mechanisms by which the population properties of hippocampal ensembles, within individual young and aged animals, may contribute to the accuracy of spatial memory; 2) to test hypotheses concerning the fundamental principle of attractor dynamics as it relates to hippocampal network behavior during aging; and 3) to examine neural correlates of sequence learning, and how behavioral deficits may arise in sequential associations in old animals. The ultimate result of such investigations will be an improved understanding of emergent ensemble properties of the aged brain that contribute to memory impairment.
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