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      A specific role for septohippocampal acetylcholine in memory?

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          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

          ► We review effects of lesion/pharmacological disruption to the cholinergic system. ► We review a model of the role of septohippocampal acetylcholine in memory. ► We review recent behavioural loss-of-function and electrophysiological data. ► We use the model to explain deficits after septohippocampal cholinergic disruption.

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          Most cited references119

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          EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis.

          Evidence is presented that EEG oscillations in the alpha and theta band reflect cognitive and memory performance in particular. Good performance is related to two types of EEG phenomena (i) a tonic increase in alpha but a decrease in theta power, and (ii) a large phasic (event-related) decrease in alpha but increase in theta, depending on the type of memory demands. Because alpha frequency shows large interindividual differences which are related to age and memory performance, this double dissociation between alpha vs. theta and tonic vs. phasic changes can be observed only if fixed frequency bands are abandoned. It is suggested to adjust the frequency windows of alpha and theta for each subject by using individual alpha frequency as an anchor point. Based on this procedure, a consistent interpretation of a variety of findings is made possible. As an example, in a similar way as brain volume does, upper alpha power increases (but theta power decreases) from early childhood to adulthood, whereas the opposite holds true for the late part of the lifespan. Alpha power is lowered and theta power enhanced in subjects with a variety of different neurological disorders. Furthermore, after sustained wakefulness and during the transition from waking to sleeping when the ability to respond to external stimuli ceases, upper alpha power decreases, whereas theta increases. Event-related changes indicate that the extent of upper alpha desynchronization is positively correlated with (semantic) long-term memory performance, whereas theta synchronization is positively correlated with the ability to encode new information. The reviewed findings are interpreted on the basis of brain oscillations. It is suggested that the encoding of new information is reflected by theta oscillations in hippocampo-cortical feedback loops, whereas search and retrieval processes in (semantic) long-term memory are reflected by upper alpha oscillations in thalamo-cortical feedback loops. Copyright 1999 Elsevier Science B.V.
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            The role of acetylcholine in learning and memory.

            Pharmacological data clearly indicate that both muscarinic and nicotinic acetylcholine receptors have a role in the encoding of new memories. Localized lesions and antagonist infusions demonstrate the anatomical locus of these cholinergic effects, and computational modeling links the function of cholinergic modulation to specific cellular effects within these regions. Acetylcholine has been shown to increase the strength of afferent input relative to feedback, to contribute to theta rhythm oscillations, activate intrinsic mechanisms for persistent spiking, and increase the modification of synapses. These effects might enhance different types of encoding in different cortical structures. In particular, the effects in entorhinal and perirhinal cortex and hippocampus might be important for encoding new episodic memories.
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              The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells.

              Using the techniques set out in the preceding paper (Muller et al., 1987), we investigated the response of place cells to changes in the animal's environment. The standard apparatus used was a cylinder, 76 cm in diameter, with walls 51 cm high. The interior was uniformly gray except for a white cue card that ran the full height of the wall and occupied 100 degrees of arc. The floor of the apparatus presented no obstacles to the animal's motions. Each of these major features of the apparatus was varied while the others were held constant. One set of manipulations involved the cue card. Rotating the cue card produced equal rotations of the firing fields of single cells. Changing the width of the card did not affect the size, shape, or radial position of firing fields, although sometimes the field rotated to a modest extent. Removing the cue card altogether also left the size, shape, and radial positions of firing fields unchanged, but caused fields to rotate to unpredictable angular positions. The second set of manipulations dealt with the size and shape of the apparatus wall. When the standard (small) cylinder was scaled up in diameter and height by a factor of 2, the firing fields of 36% of the cells observed in both cylinders also scaled, in the sense that the field stayed at the same angular position and at the same relative radial position. Of the cells recorded in both cylinders, 52% showed very different firing patterns in one cylinder than in the other. The remaining 12% of the cells were virtually silent in both cylinders. Similar results were obtained when individual cells were recorded in both a small and a large rectangular enclosure. By contrast, when the apparatus floor plan was changed from circular to rectangular, the firing pattern of a cell in an apparatus of one shape could not be predicted from a knowledge of the firing pattern in the other shape. The final manipulations involved placing vertical barriers into the otherwise unobstructed floor of the small cylinder. When an opaque barrier was set up to bisect a previously recorded firing field, in almost all cases the firing field was nearly abolished. This was true even though the barrier occupied only a small fraction of the firing field area. A transparent barrier was effective as the opaque barrier in attenuating firing fields. The lead base used to anchor the vertical barriers did not affect place cell firing.(ABSTRACT TRUNCATED AT 400 WORDS)
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                Author and article information

                Contributors
                Journal
                Neuropsychologia
                Neuropsychologia
                Neuropsychologia
                Pergamon Press
                0028-3932
                1873-3514
                1 November 2012
                November 2012
                : 50
                : 13
                : 3156-3168
                Affiliations
                Department of Psychology, University of Durham, Durham, DH1 3LE, UK
                Author notes
                Article
                NSY4581
                10.1016/j.neuropsychologia.2012.07.022
                3605586
                22884957
                3ce454be-b0a4-47de-aced-f6d370809ea3
                © 2012 Elsevier Ltd.

                This document may be redistributed and reused, subject to certain conditions.

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                Categories
                Article

                Neurology
                oscillations,theta,scopolamine,rats,episodic memory,spatial memory
                Neurology
                oscillations, theta, scopolamine, rats, episodic memory, spatial memory

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