HIPPOCAMPAL SPATIAL REPRESENTATIONS

空间能力通常会随着年龄的增长而下降

Spatial abilities are often observed to decline as a result of normal aging in both humans and rats. In the interest of the future development of appropriate therapeutic treatments, it is necessary to understand the contribution of age-related changes in brain organization. The hippocampus is a particularly interesting structure for study in this regard because it is considered critical for the acquisition of new spatial information, and it appears particularly susceptible to age-associated pathological abnormalities. Thus, the prim,dry focus of this research is to understand the relationship between physiological properties of a senescent hippocampal formation and spatial performance in rats. Since synaptic activation within hippocampus is extensively modulated by different subcortical afferents (some of which are known to undergo significant changes with age), this research will also examine the possibility that age-related changes in subcortical inputs influence the accuracy with which the hippocampus represents spatial aspects if an environment. The specific goals of this proposal is to provide a comprehensive evaluation of the contributions of neural representations of space and movement in the hippocampus to impaired spatial performance by aged rats. This goal will be accomplished in two parts: First discharge of different populations of single hippocampal neurons will be correlated with specific behaviors and spatial cognitive skills of young and old animals. Also, possible age differences in factors such as attention to spatial cues will be considered in terms of age-related changes in choice accuracy and neurophysiological function. Part 2 of this proposal will assess the effects of age on subcortical modulation of hippocampal function by monitoring behavioral and physiological consequences of selective and reversible deafferentation in young and old rats performing a spatial memory task. Seven afferent structures will be examined. Temporary deafferentation will be achieved by microinjection of a local anesthetic (tetracaine) or a GABA agonist (muscimol) into afferent nuclei. Using an injection-recording procedure that was recently developed for this research, the immediate behavioral and physiological consequences of selective deafferentation, as well as recovery back to baseline conditions. will be observed. Afferent activation effects will be tested by local injection of glutamate or carbachol. In summary, these results should provide important insight into possible age-changes in the neural representation of information critical for accurate spatial behaviors.