Muscarinic Blockade Slows and Degrades the Location-Specific Firing of Hippocampal Pyramidal Cells

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Abstract
The firing of rat hippocampal pyramidal cells is determined both by the animal's location and by the state of the hippocampal EEG. Because cholinergic transmission plays a role in EEG activity, we expected that its modification would alter place cell activity. We therefore investigated the effects on place cell activity of blocking muscarinic transmission with intracerebroventricular injections of scopolamine. Scopolamine reduced both the rate of place cell discharge inside firing fields and the spatial coherence of the fields; discharge outside of the fields also showed small increases. After injections, fields were shifted farther from their previous location than for saline controls, indicating reduced reproducibility after muscarinic blockade. Scopolamine increased the time rats were stationary, but changes in place cell activity persisted even after analysis was restricted to periods of walking, suggesting that the behavioral changes cannot account for the cell discharge changes. The scopolamine effects were dose dependent to an extent that varied between different measures. The firing rates of interneurons showed only a minor trend to decrease after scopolamine. Nevertheless, the spatial coherence of interneuron firing patterns was reduced, consistent with the recent demonstration that their positional firing is mediated by the location-specific firing of pyramids (Marshall et al., 2002). These results demonstrate that acetylcholine enhances positional firing patterns in the hippocampus. Muscarinic blockade weakens the positional firing of most place cells and therefore renders them less useful for precise representation of the environment. This effect may underlie the difficulties in spatial learning and problem solving caused by abnormalities of cholinergic transmission.