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      Cholinergic modulation of spatial learning, memory and navigation

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          Abstract

          Spatial learning, including encoding and retrieval of spatial memories as well as holding spatial information in working memory generally serving navigation under a broad range of circumstances, relies on a network of structures. While central to this network are medial temporal lobe structures with a widely appreciated crucial function of the hippocampus, neocortical areas such as the posterior parietal cortex and the retrosplenial cortex also play essential roles. Since the hippocampus receives its main subcortical input from the medial septum of the basal forebrain (BF) cholinergic system, it is not surprising that the potential role of the septo‐hippocampal pathway in spatial navigation has been investigated in many studies. Much less is known of the involvement in spatial cognition of the parallel projection system linking the posterior BF with neocortical areas. Here we review the current state of the art of the division of labour within this complex ‘navigation system’, with special focus on how subcortical cholinergic inputs may regulate various aspects of spatial learning, memory and navigation.

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          Most cited references401

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          Microstructure of a spatial map in the entorhinal cortex.

          The ability to find one's way depends on neural algorithms that integrate information about place, distance and direction, but the implementation of these operations in cortical microcircuits is poorly understood. Here we show that the dorsocaudal medial entorhinal cortex (dMEC) contains a directionally oriented, topographically organized neural map of the spatial environment. Its key unit is the 'grid cell', which is activated whenever the animal's position coincides with any vertex of a regular grid of equilateral triangles spanning the surface of the environment. Grids of neighbouring cells share a common orientation and spacing, but their vertex locations (their phases) differ. The spacing and size of individual fields increase from dorsal to ventral dMEC. The map is anchored to external landmarks, but persists in their absence, suggesting that grid cells may be part of a generalized, path-integration-based map of the spatial environment.
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            The cholinergic hypothesis of geriatric memory dysfunction.

            Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed. An attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature. Significant cholinergic dysfunctions occur in the aged and demented central nervous system, relationships between these changes and loss of memory exist, similar memory deficits can be artificially induced by blocking cholinergic mechanisms in young subjects, and under certain tightly controlled conditions reliable memory improvements in aged subjects can be achieved after cholinergic stimulation. Conventional attempts to reduce memory impairments in clinical trials hav not been therapeutically successful, however. Possible explanations for these disappointments are given and directions for future laboratory and clinical studies are suggested.
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              Place navigation impaired in rats with hippocampal lesions

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                Author and article information

                Contributors
                solari.nicola@koki.mta.hu
                hangya.balazs@koki.mta.hu
                Journal
                Eur J Neurosci
                Eur. J. Neurosci
                10.1111/(ISSN)1460-9568
                EJN
                The European Journal of Neuroscience
                John Wiley and Sons Inc. (Hoboken )
                0953-816X
                1460-9568
                19 August 2018
                September 2018
                : 48
                : 5 ( doiID: 10.1111/ejn.2018.48.issue-5 )
                : 2199-2230
                Affiliations
                [ 1 ] Lendület Laboratory of Systems Neuroscience Department of Cellular and Network Neurobiology Institute of Experimental Medicine Hungarian Academy of Sciences Budapest Hungary
                Author notes
                [*] [* ] Correspondence

                Nicola Solari and Balázs Hangya, Lendület Laboratory of Systems Neuroscience, Department of Cellular and Network Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.

                Emails: solari.nicola@ 123456koki.mta.hu ; hangya.balazs@ 123456koki.mta.hu

                Author information
                http://orcid.org/0000-0003-2709-7407
                Article
                EJN14089
                10.1111/ejn.14089
                6174978
                30055067
                42542b45-d073-488e-88d1-9addc5658197
                © 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and JohnWiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 April 2018
                : 25 June 2018
                : 23 July 2018
                Page count
                Figures: 2, Tables: 0, Pages: 32, Words: 29520
                Funding
                Funded by: Magyar Tudományos Akadémia
                Award ID: LP2015‐2/2015
                Funded by: Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal
                Award ID: KH 125294
                Funded by: H2020 European Research Council
                Award ID: ERC StG 715043
                Categories
                Review Article
                Neurosystems
                Custom metadata
                2.0
                ejn14089
                September 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.0 mode:remove_FC converted:08.10.2018

                Neurosciences
                acetylcholine,basal forebrain,hippocampus,posterior parietal cortex,retrosplenial cortex

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