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      Functional properties of stellate cells in medial entorhinal cortex layer II

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          Abstract

          Layer II of the medial entorhinal cortex (MEC) contains two principal cell types: pyramidal cells and stellate cells. Accumulating evidence suggests that these two cell types have distinct molecular profiles, physiological properties, and connectivity. The observations hint at a fundamental functional difference between the two cell populations but conclusions have been mixed. Here, we used a tTA-based transgenic mouse line to drive expression of ArchT, an optogenetic silencer, specifically in stellate cells. We were able to optogenetically identify stellate cells and characterize their firing properties in freely moving mice. The stellate cell population included cells from a range of functional cell classes. Roughly one in four of the tagged cells were grid cells, suggesting that stellate cells contribute not only to path-integration-based representation of self-location but also have other functions. The data support observations suggesting that grid cells are not the sole determinant of place cell firing.

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          Most cited references63

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          Path integration and the neural basis of the 'cognitive map'.

          The hippocampal formation can encode relative spatial location, without reference to external cues, by the integration of linear and angular self-motion (path integration). Theoretical studies, in conjunction with recent empirical discoveries, suggest that the medial entorhinal cortex (MEC) might perform some of the essential underlying computations by means of a unique, periodic synaptic matrix that could be self-organized in early development through a simple, symmetry-breaking operation. The scale at which space is represented increases systematically along the dorsoventral axis in both the hippocampus and the MEC, apparently because of systematic variation in the gain of a movement-speed signal. Convergence of spatially periodic input at multiple scales, from so-called grid cells in the entorhinal cortex, might result in non-periodic spatial firing patterns (place fields) in the hippocampus.
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            Conjunctive representation of position, direction, and velocity in entorhinal cortex.

            Grid cells in the medial entorhinal cortex (MEC) are part of an environment-independent spatial coordinate system. To determine how information about location, direction, and distance is integrated in the grid-cell network, we recorded from each principal cell layer of MEC in rats that explored two-dimensional environments. Whereas layer II was predominated by grid cells, grid cells colocalized with head-direction cells and conjunctive grid x head-direction cells in the deeper layers. All cell types were modulated by running speed. The conjunction of positional, directional, and translational information in a single MEC cell type may enable grid coordinates to be updated during self-motion-based navigation.
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              High-Performance Genetically Targetable Optical Neural Silencing via Light-Driven Proton Pumps

              The ability to silence the activity of genetically specified neurons in a temporally precise fashion would open up the ability to investigate the causal role of specific cell classes in neural computations, behaviors, and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate very powerful, safe, multiple-color silencing of neural activity. The gene archaerhodopsin-31 (Arch) from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. In addition, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally-relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins2,3 or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue-green light-drivable proton pump from the fungus Leptosphaeria maculans 4 (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue vs. red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of “optogenetic” voltage and ion modulator, which will broadly empower new neuroscientific, biological, neurological, and psychiatric investigations.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                14 September 2018
                2018
                : 7
                : e36664
                Affiliations
                [1 ]deptKavli Institute for Systems Neuroscience and Centre for Neural Computation Norwegian University of Science and Technology TrondheimNorway
                The University of Texas at Austin, Center for Learning and Memory United States
                Brown University United States
                The University of Texas at Austin, Center for Learning and Memory United States
                Boston University United States
                University College London United Kingdom
                Author information
                http://orcid.org/0000-0002-2735-2730
                Article
                36664
                10.7554/eLife.36664
                6140717
                30215597
                e59e558f-6ac0-45c1-8892-05fdabb17cca
                © 2018, Rowland et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 14 March 2018
                : 09 August 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100010663, H2020 European Research Council;
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100005416, Norges Forskningsråd;
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001706, Louis-Jeantet Foundation;
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004076, Körber-Stiftung;
                Award ID: The Körber prize
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100001201, Kavli Foundation;
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100010665, H2020 Marie Skłodowska-Curie Actions;
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Neuroscience
                Custom metadata
                Stellate cells in the medial entorhinal cortex are functionally heterogeneous but a substantial fraction are grid cells.

                Life sciences
                entorhinal cortex,stellate cells,grid cells,spatial navigation,memory,mouse
                Life sciences
                entorhinal cortex, stellate cells, grid cells, spatial navigation, memory, mouse

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