scholarly journals Functional network topography of the medial entorhinal cortex

2021 ◽  
Author(s):  
Horst A. Obenhaus ◽  
Weijian Zong ◽  
R. Irene Jacobsen ◽  
Tobias Rose ◽  
Flavio Donato ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Grid Cell ◽  
Cell Types ◽  
List Type ◽  
Head Direction ◽  
Grid Cells ◽  
Activity Data ◽  
Medial Entorhinal Cortex ◽  
Depth Analysis ◽  
Low Levels

SummaryThe medial entorhinal cortex (MEC) creates a map of local space, based on the firing patterns of grid, head direction (HD), border, and object-vector (OV) cells. How these cell types are organized anatomically is debated. In-depth analysis of this question requires collection of precise anatomical and activity data across large populations of neurons during unrestrained behavior, which neither electrophysiological nor previous imaging methods fully afford. Here we examined the topographic arrangement of spatially modulated neurons in MEC and adjacent parasubiculum using miniaturized, portable two-photon microscopes, which allow mice to roam freely in open fields. Grid cells exhibited low levels of co-occurrence with OV cells and clustered anatomically, while border, HD and OV cells tended to intermingle. These data suggest that grid-cell networks might be largely distinct from those of border, HD and OV cells and that grid cells exhibit strong coupling among themselves but weaker links to other cell types.Highlights- Grid and object vector cells show low levels of regional co-occurrence- Grid cells exhibit the strongest tendency to cluster among all spatial cell types- Grid cells stay separate from border, head direction and object vector cells- The territories of grid, head direction and border cells remain stable over weeks

scholarly journals Home, head direction stability, and grid cell distortion

2020 ◽  
Vol 123 (4) ◽  
pp. 1392-1406 ◽  
Author(s):  
Juan Ignacio Sanguinetti-Scheck ◽  
Michael Brecht
Keyword(s):  
Entorhinal Cortex ◽  
Home Cage ◽  
Cell Activity ◽  
Grid Cell ◽  
Head Direction ◽  
Grid Cells ◽  
Head Direction Cells ◽  
Medial Entorhinal Cortex ◽  
Abstract Approach ◽  
Globally Stable

The home is a unique location in the life of humans and animals. In rats, home presents itself as a multicompartmental space that involves integrating navigation through subspaces. Here we embedded the laboratory rat’s home cage in the arena, while recording neurons in the animal’s parasubiculum and medial entorhinal cortex, two brain areas encoding the animal’s location and head direction. We found that head direction signals were unaffected by home cage presence or translocation. Head direction cells remain globally stable and have similar properties inside and outside the embedded home. We did not observe egocentric bearing encoding of the home cage. However, grid cells were distorted in the presence of the home cage. While they did not globally remap, single firing fields were translocated toward the home. These effects appeared to be geometrical in nature rather than a home-specific distortion and were not dependent on explicit behavioral use of the home cage during a hoarding task. Our work suggests that medial entorhinal cortex and parasubiculum do not remap after embedding the home, but local changes in grid cell activity overrepresent the embedded space location and might contribute to navigation in complex environments. NEW & NOTEWORTHY Neural findings in the field of spatial navigation come mostly from an abstract approach that separates the animal from even a minimally biological context. In this article we embed the home cage of the rat in the environment to address some of the complexities of natural navigation. We find no explicit home cage representation. While both head direction cells and grid cells remain globally stable, we find that embedded spaces locally distort grid cells.

scholarly journals Home, head direction stability and grid cell distortion

2019 ◽  
Author(s):  
Juan Ignacio Sanguinetti-Scheck ◽  
Michael Brecht
Keyword(s):  
Entorhinal Cortex ◽  
Home Cage ◽  
Grid Cell ◽  
Neural Representation ◽  
Head Direction ◽  
Grid Cells ◽  
Medial Entorhinal Cortex ◽  
Home Location ◽  
Single Firing ◽  
Behavioral Studies

AbstractThe home is a unique location in the life of humans and animals. Numerous behavioral studies investigating homing indicate that many animals maintain an online representation of the direction of the home, a home vector. Here we placed the rat’s home cage in the arena, while recording neurons in the animal’s parasubiculum and medial entorhinal cortex. From a pellet hoarding paradigm it became evident that the home cage induced locomotion patterns characteristic of homing behaviors. We did not observe home-vector cells. We found that head-direction signals were unaffected by home location. However, grid cells were distorted in the presence of the home cage. While they did not globally remap, single firing fields were translocated towards the home. These effects appeared to be geometrical in nature rather than a home-specific distortion. Our work suggests that medial entorhinal cortex and parasubiculum do not contain an explicit neural representation of the home direction.

scholarly journals Functional connectivity of the entorhinal–hippocampal space circuit

2014 ◽  
Vol 369 (1635) ◽  
pp. 20120516 ◽  
Author(s):  
Sheng-Jia Zhang ◽  
Jing Ye ◽  
Jonathan J. Couey ◽  
Menno Witter ◽  
Edvard I. Moser ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Cell Types ◽  
Place Cells ◽  
Projection Neurons ◽  
Border Cells ◽  
Head Direction ◽  
Grid Cells ◽  
Head Direction Cells ◽  
Dynamic Interactions ◽  
Cell Groups

The mammalian space circuit is known to contain several functionally specialized cell types, such as place cells in the hippocampus and grid cells, head-direction cells and border cells in the medial entorhinal cortex (MEC). The interaction between the entorhinal and hippocampal spatial representations is poorly understood, however. We have developed an optogenetic strategy to identify functionally defined cell types in the MEC that project directly to the hippocampus. By expressing channelrhodopsin-2 (ChR2) selectively in the hippocampus-projecting subset of entorhinal projection neurons, we were able to use light-evoked discharge as an instrument to determine whether specific entorhinal cell groups—such as grid cells, border cells and head-direction cells—have direct hippocampal projections. Photoinduced firing was observed at fixed minimal latencies in all functional cell categories, with grid cells as the most abundant hippocampus-projecting spatial cell type. We discuss how photoexcitation experiments can be used to distinguish the subset of hippocampus-projecting entorhinal neurons from neurons that are activated indirectly through the network. The functional breadth of entorhinal input implied by this analysis opens up the potential for rich dynamic interactions between place cells in the hippocampus and different functional cell types in the entorhinal cortex (EC).

scholarly journals Inter- and intra-animal variation of integrative properties of stellate cells in the medial entorhinal cortex

2019 ◽  
Author(s):  
Hugh Pastoll ◽  
Derek Garden ◽  
Ioannis Papastathopoulos ◽  
Gülşen Sürmeli ◽  
Matthew F. Nolan
Keyword(s):  
Entorhinal Cortex ◽  
Ex Vivo ◽  
Spatial Scales ◽  
Phenotypic Variability ◽  
Grid Cell ◽  
Stellate Cells ◽  
Cell Types ◽  
Functional Variation ◽  
Medial Entorhinal Cortex ◽  
Nervous System Function

AbstractDistinctions between cell types underpin organisational principles for nervous system function. Functional variation also exists between neurons of the same type. This is exemplified by correspondence between grid cell spatial scales and synaptic integrative properties of stellate cells (SCs) in the medial entorhinal cortex. However, we know little about how functional variability is structured either within or between individuals. Using ex-vivo patch-clamp recordings from up to 55 SCs per mouse, we find that integrative properties vary between mice and, in contrast to modularity of grid cell spatial scales, have a continuous dorsoventral organisation. Our results constrain mechanisms for modular grid firing and provide evidence for inter-animal phenotypic variability among neurons of the same type. We suggest that neuron type properties are tuned to circuit level set points that vary within and between animals.

Entorhinal Cortex

2017 ◽  
pp. 227-244
Author(s):  
Edvard I. Moser ◽  
Menno P. Witter ◽  
May-Britt Moser
Keyword(s):  
Entorhinal Cortex ◽  
Grid Cell ◽  
Cell Types ◽  
Structure And Function ◽  
Modular Organization ◽  
Head Direction ◽  
Head Direction Cells ◽  
Terra Incognita ◽  
And Function ◽  
Hippocampal Structure

While decades of study have unraveled some of the basic principles of hippocampal structure and function, the adjacent entorhinal cortex (EC) has remained terra incognita in many respects. Recent studies suggest that the medial part of the entorhinal cortex is part of a two-dimensional metric map of the animal’s changing location in the environment. A key component of this map is the grid cell, which fires selectively at hexagonally spaced positions in the animal’s environment. Grid cells colocalize with other recently discovered medial entorhinal cell types, such as head direction cells, conjunctive grid × head direction cells, border cells, and speed cells. This chapter provides an overview of these functional cell types, their possible relationship to morphological cell types, the intrinsic architecture of the system (including laminar, longitudinal, and modular organization), and the extrinsic connectivity and possible function of both the medial and lateral subdivisions of the entorhinal cortex.

scholarly journals Functional properties of stellate cells in medial entorhinal cortex layer II

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
David C Rowland ◽  
Horst A Obenhaus ◽  
Emilie R Skytøen ◽  
Qiangwei Zhang ◽  
Cliff G Kentros ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Stellate Cell ◽  
Pyramidal Cells ◽  
Stellate Cells ◽  
Cell Types ◽  
Functional Difference ◽  
Grid Cells ◽  
Medial Entorhinal Cortex ◽  
Transgenic Mouse Line ◽  
Firing Properties

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.

scholarly journals Explaining heterogeneity in medial entorhinal cortex with task-driven neural networks

2021 ◽  
Author(s):  
Aran Nayebi ◽  
Alexander Attinger ◽  
Malcolm G. Campbell ◽  
Kiah Hardcastle ◽  
Isabel I.C. Low ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Network Architecture ◽  
Path Integration ◽  
Neuronal Response ◽  
Grid Cell ◽  
Cell Types ◽  
Neural Network Models ◽  
Medial Entorhinal Cortex ◽  
Wide Range ◽  
Response Profiles

Medial entorhinal cortex (MEC) supports a wide range of navigational and memory related behaviors. Well-known experimental results have revealed specialized cell types in MEC --- e.g. grid, border, and head-direction cells --- whose highly stereotypical response profiles are suggestive of the role they might play in supporting MEC functionality. However, the majority of MEC neurons do not exhibit stereotypical firing patterns. How should the response profiles of these more "heterogeneous" cells be described, and how do they contribute to behavior? In this work, we took a computational approach to addressing these questions. We first performed a statistical analysis that shows that heterogeneous MEC cells are just as reliable in their response patterns as the more stereotypical cell types, suggesting that they have a coherent functional role. Next, we evaluated a spectrum of candidate models in terms of their ability to describe the response profiles of both stereotypical and heterogeneous MEC cells. We found that recently developed task-optimized neural network models are substantially better than traditional grid cell-centric models at matching most MEC neuronal response profiles --- including those of grid cells themselves --- despite not being explicitly trained for this purpose. Specific choices of network architecture (such as gated nonlinearities and an explicit intermediate place cell representation) have an important effect on the ability of the model to generalize to novel scenarios, with the best of these models closely approaching the noise ceiling of the data itself. We then performed "in-silica" experiments on this model to address questions involving the relative functional relevance of various cell types, finding that heterogeneous cells are likely to be just as involved in downstream functional outcomes (such as path integration) as grid and border cells. Finally, inspired by recent data showing that, going beyond their spatial response selectivity, MEC cells are also responsive to non-spatial rewards, we introduce a new MEC model that performs reward-modulated path integration. We find that this unified model matches neural recordings across all variable-reward conditions. Taken together, our results point toward a conceptually principled goal-driven modeling approach for moving future experimental and computational efforts beyond overly-simplistic single-cell stereotypes.

scholarly journals Microcircuits for spatial coding in the medial entorhinal cortex

2021 ◽  
Author(s):  
John J Tukker ◽  
Prateep Beed ◽  
Michael Brecht ◽  
Richard Kempter ◽  
Edvard I Moser ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Hippocampal Formation ◽  
Spatial Navigation ◽  
Cell Types ◽  
Head Direction ◽  
Spatial Coding ◽  
Grid Pattern ◽  
Medial Entorhinal Cortex ◽  
Attractor Dynamics ◽  
Discharge Patterns

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.

Optogenetic Dissection of Entorhinal-Hippocampal Functional Connectivity

Science ◽  
2013 ◽  
Vol 340 (6128) ◽  
pp. 1232627 ◽  
Author(s):  
Sheng-Jia Zhang ◽  
Jing Ye ◽  
Chenglin Miao ◽  
Albert Tsao ◽  
Ignas Cerniauskas ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Entorhinal Cortex ◽  
Cell Types ◽  
Place Cell ◽  
Projection Neurons ◽  
Functional Identity ◽  
Border Cells ◽  
Head Direction ◽  
Medial Entorhinal Cortex ◽  
Adeno Associated Virus

We used a combined optogenetic-electrophysiological strategy to determine the functional identity of entorhinal cells with output to the place-cell population in the hippocampus. Channelrhodopsin-2 (ChR2) was expressed selectively in the hippocampus-targeting subset of entorhinal projection neurons by infusing retrogradely transportable ChR2-coding recombinant adeno-associated virus in the hippocampus. Virally transduced ChR2-expressing cells were identified in medial entorhinal cortex as cells that fired at fixed minimal latencies in response to local flashes of light. A large number of responsive cells were grid cells, but short-latency firing was also induced in border cells and head-direction cells, as well as cells with irregular or nonspatial firing correlates, which suggests that place fields may be generated by convergence of signals from a broad spectrum of entorhinal functional cell types.

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

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Noam Almog ◽  
Gilad Tocker ◽  
Tora Bonnevie ◽  
Edvard I Moser ◽  
May-Britt Moser ◽  
...  
Keyword(s):  
Grid Cell ◽  
Head Direction ◽  
Grid Cells ◽  
Regular Grid ◽  
Spatial Correlations ◽  
Grid Pattern ◽  
Medial Entorhinal Cortex ◽  
Cell Network ◽  
Intrinsic Connectivity ◽  
Temporal And Spatial

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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