Abstract
Acetylcholine has long been implicated in memory, including hippocampal-dependent memory, but the specific role for this neurotransmitter is difficult to identify in human neuropsychology. Here, we review the evidence for a mechanistic model of acetylcholine function within the hippocampus and consider its explanatory power for interpreting effects resulting from both pharmacological anticholinergic manipulations and lesions of the cholinergic input to the hippocampus in animals. We argue that these effects indicate that acetylcholine is necessary for some, but not all, hippocampal-dependent processes. We review recent evidence from lesion, pharmacological and electrophysiological studies to support the view that a primary function of septohippocampal acetylcholine is to reduce interference in the learning process by adaptively timing and separating encoding and retrieval processes. We reinterpret cholinergic-lesion based deficits according to this view and propose that acetylcholine reduces the interference elicited by the movement of salient locations between events.
Highlights
Acetylcholine (ACh) has long been implicated as a neurotransmitter in learning and memory (e.g. Drachman, 1977)
Recordings of CA1 pyramidal cells under manipulations of novelty and cholinergic disruption suggest that encoding and retrieval take place at different theta phases, and that this is at least partly controlled by ACh
Acetylcholine enhances those pathways that support the encoding of information inherent in the current context (‘place A’ and ‘food absence’, ‘leather’ and ‘boot’) while inhibiting those pathways subserving retrieval of different associations with some of the stimuli present in the current context (‘place A’ and ‘food presence’, ‘leather’ and ‘holster’)
Summary
ACh will be useful in reducing interference that results from a cue having more than one association over the course of a task. The ERS framework was used by Hasselmo, Stern and colleagues to successfully predict that scopolamine would more strongly impair encoding on the version of the paired-associate task where words appeared on both lists than on the version where words appeared on one list only (Atri et al, 2004). This point is underlined by looking at a completely different task, the Morris water maze used with rodents. Theta oscillations appear to be involved in both memory encoding and retrieval
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