INCREASED RESPONSIVENESS OF HIPPOCAMPAL PYRAMIDAL NEURONS TO NICOTINE IN AGED, LEARNING-IMPAIRED RATS

The effect of aging upon the responsiveness of hippocampal CA1 pyramidal neurons to nicotine was investigated using electrophysiological techniques in male Fischer 344 rats. Prior to electrophysiological recording, animals were behaviorally tested using the Morris water maze. All 3-6 and 18-21 month rats displayed rapid place learning in this task, while none of the 27 30 month animals learned within the 5-day test period. By contrast, rats of all age groups were able to learn a cue version of the water maze task. Following behavioral testing, the animals were anesthetized with sodium pentobarbital for acute recording. Nicotine was locally applied to electrophysiologically identified CA] pyramidal neurons using pressure microejection from two-barreled glass microelectrodes. For each neuron, a dose of nicotine was found which elicited a 300-400% increase in basal firing rate. These data were used to construct cumulative dose response curves for populations of neurons tested in 3-6-, 18-21 -, and 27-30-month-old animals. An age-related increase in the responsiveness of CA1 pyramidal neurons to locally applied nicotine was observed. The results of this study suggest that an increase in hippocampal CA1 pyramidal cell responsiveness to nicotine could be related to the impaired place learning ability seen with aging.