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      Development and topographical organization of projections from the hippocampus and parahippocampus to the retrosplenial cortex

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          Abstract

          The rat hippocampal formation ( HF), parahippocampal region ( PHR), and retrosplenial cortex ( RSC) play critical roles in spatial processing. These regions are interconnected, and functionally dependent. The neuronal networks mediating this reciprocal dependency are largely unknown. Establishing the developmental timing of network formation will help to understand the emergence of this dependency. We questioned whether the long‐range outputs from HFPHR to RSC in Long Evans rats develop during the same time periods as previously reported for the intrinsic HFPHR connectivity and the projections from RSC to HFPHR. The results of a series of retrograde and anterograde tracing experiments in rats of different postnatal ages show that the postnatal projections from HFPHR to RSC display low densities around birth, but develop during the first postnatal week, reaching adult‐like densities around the time of eye‐opening. Developing projections display a topographical organization similar to adult projections. We conclude that the long‐range projections from HFPHR to RSC develop in parallel with the intrinsic circuitry of HFPHR and the projections of RSC to HFPHR.

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          Most cited references50

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          Representation of geometric borders in the entorhinal cortex.

          We report the existence of an entorhinal cell type that fires when an animal is close to the borders of the proximal environment. The orientation-specific edge-apposing activity of these "border cells" is maintained when the environment is stretched and during testing in enclosures of different size and shape in different rooms. Border cells are relatively sparse, making up less than 10% of the local cell population, but can be found in all layers of the medial entorhinal cortex as well as the adjacent parasubiculum, often intermingled with head-direction cells and grid cells. Border cells may be instrumental in planning trajectories and anchoring grid fields and place fields to a geometric reference frame.
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            Spatial representation in the entorhinal cortex.

            As the interface between hippocampus and neocortex, the entorhinal cortex is likely to play a pivotal role in memory. To determine how information is represented in this area, we measured spatial modulation of neural activity in layers of medial entorhinal cortex projecting to the hippocampus. Close to the postrhinal-entorhinal border, entorhinal neurons had stable and discrete multipeaked place fields, predicting the rat's location as accurately as place cells in the hippocampus. Precise positional modulation was not observed more ventromedially in the entorhinal cortex or upstream in the postrhinal cortex, suggesting that sensory input is transformed into durable allocentric spatial representations internally in the dorsocaudal medial entorhinal cortex.
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              Speed cells in the medial entorhinal cortex.

              Grid cells in the medial entorhinal cortex have spatial firing fields that repeat periodically in a hexagonal pattern. When animals move, activity is translated between grid cells in accordance with the animal's displacement in the environment. For this translation to occur, grid cells must have continuous access to information about instantaneous running speed. However, a powerful entorhinal speed signal has not been identified. Here we show that running speed is represented in the firing rate of a ubiquitous but functionally dedicated population of entorhinal neurons distinct from other cell populations of the local circuit, such as grid, head-direction and border cells. These 'speed cells' are characterized by a context-invariant positive, linear response to running speed, and share with grid cells a prospective bias of ∼50-80 ms. Our observations point to speed cells as a key component of the dynamic representation of self-location in the medial entorhinal cortex.
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                Author and article information

                Contributors
                menno.witter@ntnu.no
                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
                25 March 2019
                July 2019
                : 50
                : 1 ( doiID: 10.1111/ejn.2019.50.issue-1 )
                : 1799-1819
                Affiliations
                [ 1 ] Kavli Institute for Systems Neuroscience Centre for Neural Computation, Egil and Pauline Braathen and Fred Kavli Center for Cortical Microcircuits NTNU Norwegian University for Science and Technology Trondheim Norway
                [ 2 ]Present address: Department of Clinical Medicine University of Tromsø—The Arctic University of Norway Tromsø Norway
                Author notes
                [*] [* ] Correspondence

                Menno P. Witter, Kavli Institute, The Faculty of Medicine and Health Sciences, NTNU, Trondheim, Norway.

                Email: menno.witter@ 123456ntnu.no

                [†]

                These authors contributed equally to this study.

                Author information
                https://orcid.org/0000-0003-0285-1637
                Article
                EJN14395
                10.1111/ejn.14395
                6767700
                30803071
                d57c9918-c21c-4c91-bc7a-062f3877a97c
                © 2019 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & 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
                : 05 September 2018
                : 30 January 2019
                : 15 February 2019
                Page count
                Figures: 11, Tables: 1, Pages: 21, Words: 12620
                Funding
                Funded by: Kavli Foundation
                Funded by: Centre for Neural Computation
                Award ID: 223262
                Funded by: NORBRAIN1
                Award ID: 197467
                Funded by: The Arctic University of Norway
                Award ID: 227769
                Categories
                Research Report
                Systems Neuroscience
                Custom metadata
                2.0
                ejn14395
                July 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.9 mode:remove_FC converted:30.09.2019

                Neurosciences
                connectivity,entorhinal cortex,parasubiculum,presubiculum,subiculum
                Neurosciences
                connectivity, entorhinal cortex, parasubiculum, presubiculum, subiculum

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