Publications by authors named "Edvard I Moser"

106 Publications

Microcircuits for spatial coding in the medial entorhinal cortex.

Physiol Rev 2021 07 13. Epub 2021 Jul 13.

Neuroscience Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany.

The hippocampal formation is critically involved in learning and memory, and contains a large proportion of neurons encoding aspects of the organism's spatial surroundings. In the medial entorhinal cortex (MEC), this includes grid cells with their distinctive hexagonal firing fields, as well as a host of other functionally defined cell types including head-direction cells, speed cells, border cells, and object vector cells. Such spatial coding emerges from the processing of external inputs by local microcircuits. However, it remains unclear exactly how local microcircuits and their dynamics within the MEC contribute to spatial discharge patterns. In this review we focus on recent investigations of intrinsic MEC connectivity, which have started to describe and quantify both excitatory and inhibitory wiring in the superficial layers of the MEC. Although the picture is far from complete, it appears that these layers contain robust recurrent connectivity that could sustain the attractor dynamics posited to underlie grid-pattern formation. These findings pave the way to a deeper understanding of the mechanisms underlying spatial navigation and memory.
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http://dx.doi.org/10.1152/physrev.00042.2020DOI Listing
July 2021

Task-dependent mixed selectivity in the subiculum.

Cell Rep 2021 May;35(8):109175

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrre s gate 9, MTFS, 7489 Trondheim, Norway. Electronic address:

CA1 and subiculum (SUB) connect the hippocampus to numerous output regions. Cells in both areas have place-specific firing fields, although they are more dispersed in SUB. Weak responses to head direction and running speed have been reported in both regions. However, how such information is encoded in CA1 and SUB and the resulting impact on downstream targets are poorly understood. Here, we estimate the tuning of simultaneously recorded CA1 and SUB cells to position, head direction, and speed. Individual neurons respond conjunctively to these covariates in both regions, but the degree of mixed representation is stronger in SUB, and more so during goal-directed spatial navigation than free foraging. Each navigational variable could be decoded with higher precision, from a similar number of neurons, in SUB than CA1. The findings point to a possible contribution of mixed-selective coding in SUB to efficient transmission of hippocampal representations to widespread brain regions.
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http://dx.doi.org/10.1016/j.celrep.2021.109175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170370PMC
May 2021

Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings.

Science 2021 04;372(6539)

UCL Queen Square Institute of Neurology, University College London, London, UK.

Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice.
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http://dx.doi.org/10.1126/science.abf4588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244810PMC
April 2021

Frequency of theta rhythm is controlled by acceleration, but not speed, in running rats.

Neuron 2021 03 9;109(6):1029-1039.e8. Epub 2021 Feb 9.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway.

The theta rhythm organizes neural activity across hippocampus and entorhinal cortex. A role for theta oscillations in spatial navigation is supported by half a century of research reporting that theta frequency encodes running speed linearly so that displacement can be estimated through theta frequency integration. We show that this relationship is an artifact caused by the fact that the speed of freely moving animals could not be systematically disentangled from acceleration. Using an experimental procedure that clamps running speed at pre-set values, we find that the theta frequency of local field potentials and spike activity is linearly related to positive acceleration, but not negative acceleration or speed. The modulation by positive-only acceleration makes rhythmic activity at theta frequency unfit as a code to compute displacement or any other kinematic variable. Temporally precise variations in theta frequency may instead serve as a mechanism for speeding up entorhinal-hippocampal computations during accelerated movement.
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http://dx.doi.org/10.1016/j.neuron.2021.01.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980093PMC
March 2021

A Brainstem Locomotor Circuit Drives the Activity of Speed Cells in the Medial Entorhinal Cortex.

Cell Rep 2020 09;32(10):108123

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrres Gate 9, 7491 Trondheim, Norway. Electronic address:

Locomotion activates an array of sensory inputs that may help build the self-position map of the medial entorhinal cortex (MEC). In this map, speed-coding neurons are thought to dynamically update representations of the animal's position. A possible origin for the entorhinal speed signal is the mesencephalic locomotor region (MLR), which is critically involved in the activation of locomotor programs. Here, we describe, in rats, a circuit connecting the pedunculopontine tegmental nucleus (PPN) of the MLR to the MEC via the horizontal limb of the diagonal band of Broca (HDB). At each level of this pathway, locomotion speed is linearly encoded in neuronal firing rates. Optogenetic activation of PPN cells drives locomotion and modulates activity of speed-modulated neurons in HDB and MEC. Our results provide evidence for a pathway by which brainstem speed signals can reach cortical structures implicated in navigation and higher-order dynamic representations of space.
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http://dx.doi.org/10.1016/j.celrep.2020.108123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487772PMC
September 2020

During hippocampal inactivation, grid cells maintain synchrony, even when the grid pattern is lost.

Elife 2019 10 17;8. Epub 2019 Oct 17.

Rappaport Faculty of Medicine and Research Institute, Technion - Israel Institute of Technology, Haifa, Israel.

The grid cell network in the medial entorhinal cortex (MEC) has been subject to thorough testing and analysis, and many theories for their formation have been suggested. To test some of these theories, we re-analyzed data from Bonnevie et al., 2013, in which the hippocampus was inactivated and grid cells were recorded in the rat MEC. We investigated whether the firing associations of grid cells depend on hippocampal inputs. Specifically, we examined temporal and spatial correlations in the firing times of simultaneously recorded grid cells before and during hippocampal inactivation. Our analysis revealed evidence of network coherence in grid cells even in the absence of hippocampal input to the MEC, both in regular grid cells and in those that became head-direction cells after hippocampal inactivation. This favors models, which suggest that phase relations between grid cells in the MEC are dependent on intrinsic connectivity within the MEC.
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http://dx.doi.org/10.7554/eLife.47147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797478PMC
October 2019

Dissociation between Postrhinal Cortex and Downstream Parahippocampal Regions in the Representation of Egocentric Boundaries.

Curr Biol 2019 08 1;29(16):2751-2757.e4. Epub 2019 Aug 1.

Rappaport Faculty of Medicine and Research Institute, Technion - Israel Institute of Technology, Haifa 31096, Israel. Electronic address:

Navigation requires the integration of many sensory inputs to form a multi-modal cognitive map of the environment, which is believed to be implemented in the hippocampal region by spatially tuned cells [1-10]. These cells encode various aspects of the environment in a world-based (allocentric) reference frame. Although the cognitive map is represented in allocentric coordinates, the environment is sensed through diverse sensory organs, mostly situated in the animal's head, and therefore represented in sensory and parietal cortices in head-centered egocentric coordinates. Yet it is not clear how and where the brain transforms these head-centered egocentric representations to map-like allocentric representations computed in the hippocampal region. Theoretical modeling has predicted a role for both egocentric and head direction (HD) information in performing an egocentric-allocentric transformation [11-15]. Here, we recorded new data and also used data from a previous study [16]. Adapting a generalized linear model (GLM) classification [17]; we show that the postrhinal cortex (POR) contains a population of pure egocentric boundary cells (EBCs), in contrast with the conjunctive EBCs × HD cells, which we found downstream mostly in the parasubiculum (PaS) and in the medial entorhinal cortex (MEC). Our finding corroborates the idea of a brain network performing an egocentric to allocentric transformation by HD cells. This is a fundamental building block in the formation of the brain's internal cognitive map.
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http://dx.doi.org/10.1016/j.cub.2019.07.007DOI Listing
August 2019

Object-vector coding in the medial entorhinal cortex.

Nature 2019 04 3;568(7752):400-404. Epub 2019 Apr 3.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

The hippocampus and the medial entorhinal cortex are part of a brain system that maps self-location during navigation in the proximal environment. In this system, correlations between neural firing and an animal's position or orientation are so evident that cell types have been given simple descriptive names, such as place cells, grid cells, border cells and head-direction cells. While the number of identified functional cell types is growing at a steady rate, insights remain limited by an almost-exclusive reliance on recordings from rodents foraging in empty enclosures that are different from the richly populated, geometrically irregular environments of the natural world. In environments that contain discrete objects, animals are known to store information about distance and direction to those objects and to use this vector information to guide navigation. Theoretical studies have proposed that such vector operations are supported by neurons that use distance and direction from discrete objects or boundaries to determine the animal's location, but-although some cells with vector-coding properties may be present in the hippocampus and subiculum-it remains to be determined whether and how vectorial operations are implemented in the wider neural representation of space. Here we show that a large fraction of medial entorhinal cortex neurons fire specifically when mice are at given distances and directions from spatially confined objects. These 'object-vector cells' are tuned equally to a spectrum of discrete objects, irrespective of their location in the test arena, as well as to a broad range of dimensions and shapes, from point-like objects to extended surfaces. Our findings point to vector coding as a predominant form of position coding in the medial entorhinal cortex.
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http://dx.doi.org/10.1038/s41586-019-1077-7DOI Listing
April 2019

Correlation structure of grid cells is preserved during sleep.

Nat Neurosci 2019 04 25;22(4):598-608. Epub 2019 Mar 25.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway.

The network of grid cells in the medial entorhinal cortex (MEC) forms a fixed reference frame for mapping physical space. The mechanistic origin of the grid representation is unknown, but continuous attractor network models explain multiple fundamental features of grid cell activity. An untested prediction of these models is that the grid cell network should exhibit an activity correlation structure that transcends behavioral states. By recording from MEC cell ensembles during navigation and sleep, we found that spatial phase offsets of grid cells predict arousal-state-independent spike rate correlations. Similarly, state-invariant correlations between conjunctive grid-head direction and pure head direction cells were predicted by their head direction tuning offsets during awake behavior. Grid cells were only weakly correlated across grid modules, and module scale relationships disintegrated during slow-wave sleep, suggesting that grid modules function as independent attractor networks. Collectively, our observations imply that network states in MEC are expressed universally across brain and behavior states.
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http://dx.doi.org/10.1038/s41593-019-0360-0DOI Listing
April 2019

Grid-Cell Distortion along Geometric Borders.

Curr Biol 2019 03 7;29(6):1047-1054.e3. Epub 2019 Mar 7.

Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology, MTFS, Olav Kyrres gate 9, NO-7489 Trondheim, Norway. Electronic address:

Grid cells fire in a triangular pattern that tessellates the environment [1]. The pattern displays a global distortion that is well described by a shearing transformation of an idealized grid [2]. However, in addition, distortions often differ across parts of the environment, suggesting that the grid interacts with the environment locally [2-5]. How this occurs is poorly understood. To further determine the nature of local distortions, we therefore analyzed the local spatial characteristics of the grid pattern. When rats ran in a large square enclosure, the grid pattern displayed several stereotypical distortions in relation to features of the environment. These distortions were stronger at edges than on open surfaces. Curved axis orientations and distortions of the grid pattern in the corners could be explained by a geometrical model where the pattern, in conjunction with being sheared, is compressed along the walls of the enclosure. The grid compression coincided with stereotypical running behavior where the animals moved faster in the areas where the grid had the most pronounced distortions. However, neither running direction nor speed influenced the distortions on a moment-to-moment basis, raising the possibility that the distortions are a learned feature.
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http://dx.doi.org/10.1016/j.cub.2019.01.074DOI Listing
March 2019

Navigating cognition: Spatial codes for human thinking.

Science 2018 11;362(6415)

Kavli Institute for Systems Neuroscience, Centre for Neural Computation, The Egil and Pauline Braathen and Fred Kavli Centre for Cortical Microcircuits, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

The hippocampal formation has long been suggested to underlie both memory formation and spatial navigation. We discuss how neural mechanisms identified in spatial navigation research operate across information domains to support a wide spectrum of cognitive functions. In our framework, place and grid cell population codes provide a representational format to map variable dimensions of cognitive spaces. This highly dynamic mapping system enables rapid reorganization of codes through remapping between orthogonal representations across behavioral contexts, yielding a multitude of stable cognitive spaces at different resolutions and hierarchical levels. Action sequences result in trajectories through cognitive space, which can be simulated via sequential coding in the hippocampus. In this way, the spatial representational format of the hippocampal formation has the capacity to support flexible cognition and behavior.
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http://dx.doi.org/10.1126/science.aat6766DOI Listing
November 2018

Functional properties of stellate cells in medial entorhinal cortex layer II.

Elife 2018 09 14;7. Epub 2018 Sep 14.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway.

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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http://dx.doi.org/10.7554/eLife.36664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140717PMC
September 2018

Integrating time from experience in the lateral entorhinal cortex.

Nature 2018 09 29;561(7721):57-62. Epub 2018 Aug 29.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, NTNU, Trondheim, Norway.

The encoding of time and its binding to events are crucial for episodic memory, but how these processes are carried out in hippocampal-entorhinal circuits is unclear. Here we show in freely foraging rats that temporal information is robustly encoded across time scales from seconds to hours within the overall population state of the lateral entorhinal cortex. Similarly pronounced encoding of time was not present in the medial entorhinal cortex or in hippocampal areas CA3-CA1. When animals' experiences were constrained by behavioural tasks to become similar across repeated trials, the encoding of temporal flow across trials was reduced, whereas the encoding of time relative to the start of trials was improved. The findings suggest that populations of lateral entorhinal cortex neurons represent time inherently through the encoding of experience. This representation of episodic time may be integrated with spatial inputs from the medial entorhinal cortex in the hippocampus, allowing the hippocampus to store a unified representation of what, where and when.
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http://dx.doi.org/10.1038/s41586-018-0459-6DOI Listing
September 2018

Supramammillary Nucleus Modulates Spike-Time Coordination in the Prefrontal-Thalamo-Hippocampal Circuit during Navigation.

Neuron 2018 08;99(3):576-587.e5

Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology, Olav Kyrres Gate 9, MTFS, 7489 Trondheim, Norway. Electronic address:

During navigation, hippocampal spatial maps are thought to interact with action-planning systems in other regions of cortex. We here report a key role for spike-time coordination in functional coupling of the medial prefrontal cortex (mPFC) to the hippocampus through the thalamic nucleus reuniens (NR). When rats perform a T-maze alternation task, spikes of neurons in mPFC and NR exhibit enhanced coordination to the CA1 theta rhythm before the choice point on the maze. A similar coordination to CA1 theta rhythm was observed in neurons of the supramammillary nucleus (SUM). Optogenetic silencing of SUM neurons reduced the temporal coordination in the mPFC-NR-CA1 circuit. Following SUM inactivation, trajectory representations were impaired in both NR and CA1, but not in mPFC, indicating a failure in transmission of action plans from mPFC to the hippocampus. The findings identify theta-frequency spike-time coordination as a mechanism for gating of information flow in the mPFC-NR-CA1 circuit.
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http://dx.doi.org/10.1016/j.neuron.2018.07.021DOI Listing
August 2018

Entorhinal fast-spiking speed cells project to the hippocampus.

Proc Natl Acad Sci U S A 2018 02 31;115(7):E1627-E1636. Epub 2018 Jan 31.

Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology, 7489 Trondheim, Norway;

The mammalian positioning system contains a variety of functionally specialized cells in the medial entorhinal cortex (MEC) and the hippocampus. In order for cells in these systems to dynamically update representations in a way that reflects ongoing movement in the environment, they must be able to read out the current speed of the animal. Speed is encoded by speed-responsive cells in both MEC and hippocampus, but the relationship between the two populations has not been determined. We show here that many entorhinal speed cells are fast-spiking putative GABAergic neurons. Using retrograde viral labeling from the hippocampus, we find that a subset of these fast-spiking MEC speed cells project directly to hippocampal areas. This projection contains parvalbumin (PV) but not somatostatin (SOM)-immunopositive cells. The data point to PV-expressing GABAergic projection neurons in MEC as a source for widespread speed modulation and temporal synchronization in entorhinal-hippocampal circuits for place representation.
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http://dx.doi.org/10.1073/pnas.1720855115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816210PMC
February 2018

Path integration in place cells of developing rats.

Proc Natl Acad Sci U S A 2018 02 30;115(7):E1637-E1646. Epub 2018 Jan 30.

Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology, NO-7489 Trondheim, Norway;

Place cells in the hippocampus and grid cells in the medial entorhinal cortex rely on self-motion information and path integration for spatially confined firing. Place cells can be observed in young rats as soon as they leave their nest at around 2.5 wk of postnatal life. In contrast, the regularly spaced firing of grid cells develops only after weaning, during the fourth week. In the present study, we sought to determine whether place cells are able to integrate self-motion information before maturation of the grid-cell system. Place cells were recorded on a 200-cm linear track while preweaning, postweaning, and adult rats ran on successive trials from a start wall to a box at the end of a linear track. The position of the start wall was altered in the middle of the trial sequence. When recordings were made in complete darkness, place cells maintained fields at a fixed distance from the start wall regardless of the age of the animal. When lights were on, place fields were determined primarily by external landmarks, except at the very beginning of the track. This shift was observed in both young and adult animals. The results suggest that preweaning rats are able to calculate distances based on information from self-motion before the grid-cell system has matured to its full extent.
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http://dx.doi.org/10.1073/pnas.1719054115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816199PMC
February 2018

Integration of grid maps in merged environments.

Nat Neurosci 2018 01 11;21(1):92-101. Epub 2017 Dec 11.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway.

Natural environments are represented by local maps of grid cells and place cells that are stitched together. The manner by which transitions between map fragments are generated is unknown. We recorded grid cells while rats were trained in two rectangular compartments, A and B (each 1 m × 2 m), separated by a wall. Once distinct grid maps were established in each environment, we removed the partition and allowed the rat to explore the merged environment (2 m × 2 m). The grid patterns were largely retained along the distal walls of the box. Nearer the former partition line, individual grid fields changed location, resulting almost immediately in local spatial periodicity and continuity between the two original maps. Grid cells belonging to the same grid module retained phase relationships during the transformation. Thus, when environments are merged, grid fields reorganize rapidly to establish spatial periodicity in the area where the environments meet.
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http://dx.doi.org/10.1038/s41593-017-0036-6DOI Listing
January 2018

Spatial representation in the hippocampal formation: a history.

Nat Neurosci 2017 Oct;20(11):1448-1464

Center for the Neurobiology of Learning and Memory, University of California at Irvine, Irvine California, USA, and the Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada.

Since the first place cell was recorded and the cognitive-map theory was subsequently formulated, investigation of spatial representation in the hippocampal formation has evolved in stages. Early studies sought to verify the spatial nature of place cell activity and determine its sensory origin. A new epoch started with the discovery of head direction cells and the realization of the importance of angular and linear movement-integration in generating spatial maps. A third epoch began when investigators turned their attention to the entorhinal cortex, which led to the discovery of grid cells and border cells. This review will show how ideas about integration of self-motion cues have shaped our understanding of spatial representation in hippocampal-entorhinal systems from the 1970s until today. It is now possible to investigate how specialized cell types of these systems work together, and spatial mapping may become one of the first cognitive functions to be understood in mechanistic detail.
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http://dx.doi.org/10.1038/nn.4653DOI Listing
October 2017

Parvalbumin and Somatostatin Interneurons Control Different Space-Coding Networks in the Medial Entorhinal Cortex.

Cell 2017 Oct 28;171(3):507-521.e17. Epub 2017 Sep 28.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrres Gate 9, MTFS, 7489 Trondheim, Norway. Electronic address:

The medial entorhinal cortex (MEC) contains several discrete classes of GABAergic interneurons, but their specific contributions to spatial pattern formation in this area remain elusive. We employed a pharmacogenetic approach to silence either parvalbumin (PV)- or somatostatin (SOM)-expressing interneurons while MEC cells were recorded in freely moving mice. PV-cell silencing antagonized the hexagonally patterned spatial selectivity of grid cells, especially in layer II of MEC. The impairment was accompanied by reduced speed modulation in colocalized speed cells. Silencing SOM cells, in contrast, had no impact on grid cells or speed cells but instead decreased the spatial selectivity of cells with discrete aperiodic firing fields. Border cells and head direction cells were not affected by either intervention. The findings point to distinct roles for PV and SOM interneurons in the local dynamics underlying periodic and aperiodic firing in spatially modulated cells of the MEC. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.cell.2017.08.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651217PMC
October 2017

Stellate cells drive maturation of the entorhinal-hippocampal circuit.

Science 2017 03 2;355(6330). Epub 2017 Feb 2.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrres gate 9, Norwegian Brain Centre, 7491 Trondheim, Norway.

The neural representation of space relies on a network of entorhinal-hippocampal cell types with firing patterns tuned to different abstract features of the environment. To determine how this network is set up during early postnatal development, we monitored markers of structural maturation in developing mice, both in naïve animals and after temporally restricted pharmacogenetic silencing of specific cell populations. We found that entorhinal stellate cells provide an activity-dependent instructive signal that drives maturation sequentially and unidirectionally through the intrinsic circuits of the entorhinal-hippocampal network. The findings raise the possibility that a small number of autonomously developing neuronal populations operate as intrinsic drivers of maturation across widespread regions of the cortex.
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http://dx.doi.org/10.1126/science.aai8178DOI Listing
March 2017

Hippocampus at 25.

Hippocampus 2016 10 29;26(10):1238-49. Epub 2016 Jul 29.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway.

The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hipo.22616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367855PMC
October 2016

Neuroscience: Virtual reality explored.

Nature 2016 05 11;533(7603):324-5. Epub 2016 May 11.

Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology, 7491 Trondheim, Norway.

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http://dx.doi.org/10.1038/nature17899DOI Listing
May 2016

Ten Years of Grid Cells.

Annu Rev Neurosci 2016 07 9;39:19-40. Epub 2016 Mar 9.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, 7491 Trondheim, Norway; email: , , ,

The medial entorhinal cortex (MEC) creates a neural representation of space through a set of functionally dedicated cell types: grid cells, border cells, head direction cells, and speed cells. Grid cells, the most abundant functional cell type in the MEC, have hexagonally arranged firing fields that tile the surface of the environment. These cells were discovered only in 2005, but after 10 years of investigation, we are beginning to understand how they are organized in the MEC network, how their periodic firing fields might be generated, how they are shaped by properties of the environment, and how they interact with the rest of the MEC network. The aim of this review is to summarize what we know about grid cells and point out where our knowledge is still incomplete.
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http://dx.doi.org/10.1146/annurev-neuro-070815-013824DOI Listing
July 2016

Hippocampal Remapping after Partial Inactivation of the Medial Entorhinal Cortex.

Neuron 2015 Nov;88(3):590-603

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrres Gate 9, Norwegian Brain Centre, 7489 Trondheim, Norway. Electronic address:

Hippocampal place cells undergo remapping when the environment is changed. The mechanism of hippocampal remapping remains elusive but spatially modulated cells in the medial entorhinal cortex (MEC) have been identified as a possible contributor. Using pharmacogenetic and optogenetic approaches, we tested the role of MEC cells by examining in mice whether partial inactivation in MEC shifts hippocampal activity to a different subset of place cells with different receptive fields. The pharmacologically selective designer Gi-protein-coupled muscarinic receptor hM4D or the light-responsive microbial proton pump archaerhodopsin (ArchT) was expressed in MEC, and place cells were recorded after application of the inert ligand clozapine-N-oxide (CNO) or light at appropriate wavelengths. CNO or light caused partial inactivation of the MEC. The inactivation was followed by substantial remapping in the hippocampus, without disruption of the spatial firing properties of individual neurons. The results point to MEC input as an element of the mechanism for remapping in place cells.
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http://dx.doi.org/10.1016/j.neuron.2015.09.051DOI Listing
November 2015

Topography of Place Maps along the CA3-to-CA2 Axis of the Hippocampus.

Neuron 2015 Sep 19;87(5):1078-92. Epub 2015 Aug 19.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrres Gate 9, MTFS, 7489 Trondheim, Norway. Electronic address:

We asked whether the structural heterogeneity of the hippocampal CA3-CA2 axis is reflected in how space is mapped onto place cells in CA3-CA2. Place fields were smaller and sharper in proximal CA3 than in distal CA3 and CA2. The proximodistal shift was accompanied by a progressive loss in the ability of place cells to distinguish configurations of the same spatial environment, as well as a reduction in the extent to which place cells formed uncorrelated representations for different environments. The transition to similar representations was nonlinear, with the sharpest drop in distal CA3. These functional changes along the CA3-CA2 axis mirror gradients in gene expression and connectivity that partly override cytoarchitectonic boundaries between the subfields of the hippocampus. The results point to the CA3-CA2 axis as a functionally graded system with powerful pattern separation at the proximal end, near the dentate gyrus, and stronger pattern completion at the CA2 end.
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http://dx.doi.org/10.1016/j.neuron.2015.07.007DOI Listing
September 2015

Speed cells in the medial entorhinal cortex.

Nature 2015 Jul 15;523(7561):419-24. Epub 2015 Jul 15.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrres gate 9, MTFS, 7491 Trondheim, Norway.

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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http://dx.doi.org/10.1038/nature14622DOI Listing
July 2015

A prefrontal-thalamo-hippocampal circuit for goal-directed spatial navigation.

Nature 2015 Jun 27;522(7554):50-5. Epub 2015 May 27.

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrres gate 9, MTFS, 7491 Trondheim, Norway.

Spatial navigation requires information about the relationship between current and future positions. The activity of hippocampal neurons appears to reflect such a relationship, representing not only instantaneous position but also the path towards a goal location. However, how the hippocampus obtains information about goal direction is poorly understood. Here we report a prefrontal-thalamic neural circuit that is required for hippocampal representation of routes or trajectories through the environment. Trajectory-dependent firing was observed in medial prefrontal cortex, the nucleus reuniens of the thalamus, and the CA1 region of the hippocampus in rats. Lesioning or optogenetic silencing of the nucleus reuniens substantially reduced trajectory-dependent CA1 firing. Trajectory-dependent activity was almost absent in CA3, which does not receive nucleus reuniens input. The data suggest that projections from medial prefrontal cortex, via the nucleus reuniens, are crucial for representation of the future path during goal-directed behaviour and point to the thalamus as a key node in networks for long-range communication between cortical regions involved in navigation.
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http://dx.doi.org/10.1038/nature14396DOI Listing
June 2015

Shearing-induced asymmetry in entorhinal grid cells.

Nature 2015 Feb;518(7538):207-12

Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Olav Kyrres gate 9, 7491 Trondheim, Norway.

Grid cells are neurons with periodic spatial receptive fields (grids) that tile two-dimensional space in a hexagonal pattern. To provide useful information about location, grids must be stably anchored to an external reference frame. The mechanisms underlying this anchoring process have remained elusive. Here we show in differently sized familiar square enclosures that the axes of the grids are offset from the walls by an angle that minimizes symmetry with the borders of the environment. This rotational offset is invariably accompanied by an elliptic distortion of the grid pattern. Reversing the ellipticity analytically by a shearing transformation removes the angular offset. This, together with the near-absence of rotation in novel environments, suggests that the rotation emerges through non-coaxial strain as a function of experience. The systematic relationship between rotation and distortion of the grid pattern points to shear forces arising from anchoring to specific geometric reference points as key elements of the mechanism for alignment of grid patterns to the external world.
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http://dx.doi.org/10.1038/nature14151DOI Listing
February 2015

Place cells, grid cells, and memory.

Cold Spring Harb Perspect Biol 2015 Feb 2;7(2):a021808. Epub 2015 Feb 2.

Centre for Neural Computation, Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology, 7489 Trondheim, Norway.

The hippocampal system is critical for storage and retrieval of declarative memories, including memories for locations and events that take place at those locations. Spatial memories place high demands on capacity. Memories must be distinct to be recalled without interference and encoding must be fast. Recent studies have indicated that hippocampal networks allow for fast storage of large quantities of uncorrelated spatial information. The aim of the this article is to review and discuss some of this work, taking as a starting point the discovery of multiple functionally specialized cell types of the hippocampal-entorhinal circuit, such as place, grid, and border cells. We will show that grid cells provide the hippocampus with a metric, as well as a putative mechanism for decorrelation of representations, that the formation of environment-specific place maps depends on mechanisms for long-term plasticity in the hippocampus, and that long-term spatiotemporal memory storage may depend on offline consolidation processes related to sharp-wave ripple activity in the hippocampus. The multitude of representations generated through interactions between a variety of functionally specialized cell types in the entorhinal-hippocampal circuit may be at the heart of the mechanism for declarative memory formation.
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http://dx.doi.org/10.1101/cshperspect.a021808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315928PMC
February 2015
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