Cholinergic input to the hippocampus is not required for a model of episodic memory in the rat, even with multiple consecutive events

Abstract

Previous work has shown that depletion of the cholinergic input to the hippocampus produces no impairment in an episodic (what-where-which) memory task in rats. However, in contrast a where-which task was significantly impaired. Models of acetylcholine function related to pattern separation were used to explain this result. Recent development of spontaneous recognition tasks to assess multiple trials consecutively in the same testing session allow an opportunity to assess whether an increase in interference produces an impairment in the episodic memory task using the same cholinergic lesion. By increasing the number of trials happening consecutively the proactive interference between events being remembered increases, with the prediction that a reduction in pattern separation as a result of reduced acetylcholine in the hippocampus would now produce an impairment in this task. We show that a continual trials approach to the episodic memory task has no impact on the effects of cholinergic depletion of the hippocampus, with effects mirroring those from using just one trial a day approaches to these tasks. We suggest that pattern separation models of acetylcholine function can still explain our findings, but with an apparent emphasis on context-specific locations rather than all types of memory.

Continual Trials Spontaneous Recognition Tasks in Mice: Reducing Animal Numbers and Improving Our Understanding of the Mechanisms Underlying Memory

“…The apparatus used in this experiment was modified from the continual trials spontaneous recognition apparatus for rats (Ameen-Ali et al, 2012 ; Seel et al, 2017 ) and adapted in size for use with mice. A rectangular area (50 cm × 42 cm × 20 cm) comprised of a holding area and an object area.…”

“…For each animal a session constituted 16 trials. As with the continual trials approach in rats (Ameen-Ali et al, 2012 ; Seel et al, 2017 ) the number of trials is not limited due to potential performance of the animals. We see no evidence that animals’ exploration or engagement with the task is different on trial 16 to trial 1.…”

“…In recent years, we have demonstrated a novel approach to spontaneous recognition tasks in rats that have improved behavioral reliability and thus allowed reduced use of animals (Ameen-Ali et al, 2012 ; Seel et al, 2017 ). This continual trials approach both increases the number of trials completed by an animal within a single session, and by removing within-session handling of animals, minimizes handling induced stress.…”

“…This continual trials approach both increases the number of trials completed by an animal within a single session, and by removing within-session handling of animals, minimizes handling induced stress. Not only do these tasks offer a way of reducing behavioral variability and therefore improve reliability of the results, they also offer new windows into the mechanisms involved in these tasks, for example allowing the study of interference in these tasks over multiple consecutive trials (Seel et al, 2017 ).…”

“…Although the value of these new approaches have been demonstrated in rats (Ameen-Ali et al, 2012 ; Seel et al, 2017 ), increasing use of transgenic mouse models of disease suggest that there is significant benefit in additionally applying these new approaches in mice. Here, we show that an adapted version of the continual trials apparatus can be used successfully in groups of c57 and (later) in transgenic TASTPM mice.…”