Effects of intraseptal carbachol on firing characteristics of hippocampal CA1 place cells.

摘要

It had been known for decades that the hippocampus is involved in learning and memory. When an animal moves through an environment, the firing patterns of hippocampal pyramidal cells show spatial specificity or "place fields". When a rat is exposed to a familiar environment, the hippocampus displays the previously stored pattern for that environment; when the rat is introduced to a novel environment, a new pattern is displayed. It is hypothesized that the medial septal theta rhythm is the signal that switches the hippocampal activity from a recalling to an encoding state. The projection from the medial septum to the hippocampus has been shown to influence hippocampal electrophysiology, both in terms of population and single unit activity. Alteration of the septo-hippocampal input (by septal lesions, inactivation, or infusions of anticholinergic drugs) decreases hippocampal theta power, and intraseptal cholinomimetics increase hippocampal theta power. I infused a cholinergie agonist known to induce hippocampal theta into the medial septum, and recorded hippocampal CA1 pyramidal cells in young and old rats. The recordings were performed either in a familiar environment or in a novel configuration of the environment. I found a differential effect of medial septal activation under familiar and novel conditions; in young animals carbachol always caused instability of the hippocampal representation, while in aged animals carbachol caused instability in a familiar environment but improved the development of a representation under conditions of novelty. I propose that in a familiar environment CA1 cells reflect the previously stored CA3 input, and ignore minor sensory mismatches (small changes in auditory, olfactory, or visual stimuli). Increasing the degree of mismatch by moderately modifying the environment (i.e. our novel configuration) or increasing the septal modulation in a familiar environment results in CA1 reflecting extra-hippocampal input more than the previously stored CA3 input. A moderate modification of the environment accompanied by septal activity (signaling the significance of the situation) will also affect the CA3 representation, and will produce a new representation in the CA1 cell population.