Place cell assemblies remain intact, despite reduced phase precession, after cholinergic disruption

The hippocampal theta rhythm is frequently viewed as a clocking mechanism that coordinates the spiking activity of neurons across the hippocampus to form coherent neural assemblies. Phase precession is a form of temporal coding evidencing this mechanism and is degraded following systemic pharmacological disruption of cholinergic signaling. However, whether neural assemblies are commensurately degraded, as would be predicted from a clocking mechanism hypothesis, remains unknown. To address this, we recorded the spiking activity of hippocampal place cells as rats completed laps on a circle track for chocolate drink before versus during the influence of a systemic muscarinic acetylcholine receptor antagonist. We compared the integrity of hippocampal ensembles using three approaches. The first approach used cross-correlogram (CCG) analyses to ask if the relative spike-timing between pairs of cells became less reliable. The second used a general linear model based analysis to ask whether the activity of simultaneously recorded neurons became any less predictive of the spiking activity of single neurons. Finally, the third approach used a reconstruction analysis to ask if the population activity was any less informative regarding the environmental position of the animal and whether theta sequences were impaired. The results of all three analyses paint a consistent picture: systemic cholinergic disruption did not degrade assembly integrity. These data demonstrate that place cell assemblies do not depend upon high quality phase precession.