The Experts below are selected from a list of 15336 Experts worldwide ranked by ideXlab platform
Edvard I. Moser - One of the best experts on this subject based on the ideXlab platform.
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Object-vector coding in the medial Entorhinal Cortex
Nature, 2019Co-Authors: Oyvind Arne Hoydal, Emilie Ranheim Skytoen, Maybritt Moser, Sebastian Ola Andersson, Edvard I. MoserAbstract:The hippocampus and the medial Entorhinal Cortex are part of a brain system that maps self-location during navigation in the proximal environment1,2. 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 cells3, grid cells4, border cells5,6 and head-direction cells7. 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 navigation8–10. Theoretical studies have proposed that such vector operations are supported by neurons that use distance and direction from discrete objects11,12 or boundaries13,14 to determine the animal’s location, but—although some cells with vector-coding properties may be present in the hippocampus15 and subiculum16,17—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. Cells in the mouse medial Entorhinal Cortex that fire when mice are at a specific distance and direction from a stationary object suggest that vector coding is important for rodent navigation.
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integrating time from experience in the lateral Entorhinal Cortex
Nature, 2018Co-Authors: Albert Tsao, Maybritt Moser, Jorgen Sugar, Cheng Wang, James J Knierim, Edvard I. MoserAbstract: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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speed cells in the medial Entorhinal Cortex
Nature, 2015Co-Authors: Emilio Kropff, Maybritt Moser, James E. Carmichael, Edvard I. MoserAbstract: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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Speed cells in the medial Entorhinal Cortex
Nature, 2015Co-Authors: Emilio Kropff, Maybritt Moser, James E. Carmichael, Edvard I. MoserAbstract: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. On the basis of neural firing rates a specific class of neuron is identified in the medial Entorhinal Cortex that linearly encodes information on running speed in a context-independent manner and that is distinct from other functionally specific Entorhinal neurons. It has long been postulated that in the Entorhinal Cortex, grid cells require information on the running speed of the animal in order to properly encode periodic spatial firing fields as an animal moves through its environment. However, the source of such a signal transmitting speed information has not been previously identified. Here, Edvard Moser and colleagues isolate a specific class of neurons in the medial Entorhinal Cortex (MEC) that encode information linearly on running speed based on neural firing rates. These 'speed cells' are distinct from other functionally specific MEC neurons and encode speed in a context-independent manner.
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traces of experience in the lateral Entorhinal Cortex
Current Biology, 2013Co-Authors: Albert Tsao, Maybritt Moser, Edvard I. MoserAbstract:Summary A growing body of evidence suggests that memories are stored in the hippocampus by integrating spatial information from specialized cell types in the medial Entorhinal Cortex (MEC) with nonspatial information from cells in the lateral Entorhinal Cortex (LEC) [1–5]. LEC neurons show little spatial modulation when rats run in empty open-field environments [6, 7] but fire in the vicinity of discrete objects [7], suggesting that they provide information about the specific content of the spatial environment. It is unclear, however, whether firing at objects is elicited purely by stimulus properties, in a sensory-like manner, or whether any higher-order property, such as the history of experience, is also relevant. To address this question, we recorded from LEC neurons in an open field where objects were present on a subset of the trials. Whereas some neurons fired at the objects, other cells developed specific firing at places where objects had been located on previous trials, providing a readout of past experience in the environment. The latter cells generally did not respond to the object when it was present, suggesting that object cells and object-trace cells are independent cell classes. These findings identify LEC as a component of the hippocampal-cortical circuit for object-place memory.
Marilyn S Albert - One of the best experts on this subject based on the ideXlab platform.
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Entorhinal Cortex antemortem cortical thickness and postmortem neurofibrillary tangles and amyloid pathology
American Journal of Neuroradiology, 2017Co-Authors: Ashesh A Thaker, Brent D Weinberg, William P Dillon, Christopher P Hess, Howard Cabral, Debra A Fleischman, Sue Leurgans, David A Bennett, Bradley T Hyman, Marilyn S AlbertAbstract:Author(s): Thaker, AA; Weinberg, BD; Dillon, WP; Hess, CP; Cabral, HJ; Fleischman, DA; Leurgans, SE; Bennett, DA; Hyman, BT; Albert, MS; Killiany, RJ; Fischl, B; Dale, AM; Desikan, RS | Abstract: The Entorhinal Cortex, a critical gateway between the neoCortex and hippocampus, is one of the earliest regions affected by Alzheimer disease-associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging-based measure of the Entorhinal Cortex, whether antemortem Entorhinal Cortex thickness is associated with postmortem tangle burden within the Entorhinal Cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of Entorhinal Cortex thickness and postmortem neuropathological measures.We evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the Entorhinal Cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between Entorhinal Cortex thickness and tangles and amyloid-β load within the Entorhinal Cortex and medial temporal and neocortical regions.We found a significant relationship between antemortem Entorhinal Cortex thickness and Entorhinal Cortex (P = .006) and medial temporal lobe tangles (P = .002); we found no relationship between Entorhinal Cortex thickness and Entorhinal Cortex (P = .09) and medial temporal lobe amyloid-β (P = .09). We also found a significant association between Entorhinal Cortex thickness and cortical tangles (P = .003) and amyloid-β (P = .01). We found no relationship between parahippocampal gyrus thickness and Entorhinal Cortex (P = .31) and medial temporal lobe tangles (P = .051).Our findings indicate that Entorhinal Cortex-associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology.
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Entorhinal Cortex antemortem cortical thickness and postmortem neurofibrillary tangles and amyloid pathology
American Journal of Neuroradiology, 2017Co-Authors: Ashesh A Thaker, Brent D Weinberg, William P Dillon, Christopher P Hess, Howard Cabral, Debra A Fleischman, Sue Leurgans, David A Bennett, Bradley T Hyman, Marilyn S AlbertAbstract:BACKGROUND AND PURPOSE: The Entorhinal Cortex, a critical gateway between the neoCortex and hippocampus, is one of the earliest regions affected by Alzheimer disease–associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging–based measure of the Entorhinal Cortex, whether antemortem Entorhinal Cortex thickness is associated with postmortem tangle burden within the Entorhinal Cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of Entorhinal Cortex thickness and postmortem neuropathological measures. MATERIALS AND METHODS: We evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the Entorhinal Cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between Entorhinal Cortex thickness and tangles and amyloid-β load within the Entorhinal Cortex and medial temporal and neocortical regions. RESULTS: We found a significant relationship between antemortem Entorhinal Cortex thickness and Entorhinal Cortex (P = .006) and medial temporal lobe tangles (P = .002); we found no relationship between Entorhinal Cortex thickness and Entorhinal Cortex (P = .09) and medial temporal lobe amyloid-β (P = .09). We also found a significant association between Entorhinal Cortex thickness and cortical tangles (P = .003) and amyloid-β (P = .01). We found no relationship between parahippocampal gyrus thickness and Entorhinal Cortex (P = .31) and medial temporal lobe tangles (P = .051). CONCLUSIONS: Our findings indicate that Entorhinal Cortex–associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology.
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Entorhinal Cortex antemortem cortical thickness and postmortem neurofibrillary tangles and amyloid pathology
American Journal of Neuroradiology, 2017Co-Authors: Ashesh A Thaker, Brent D Weinberg, William P Dillon, Christopher P Hess, Howard Cabral, Debra A Fleischman, Sue Leurgans, David A Bennett, Bradley T Hyman, Marilyn S AlbertAbstract:Author(s): Thaker, AA; Weinberg, BD; Dillon, WP; Hess, CP; Cabral, HJ; Fleischman, DA; Leurgans, SE; Bennett, DA; Hyman, BT; Albert, MS; Killiany, RJ; Fischl, B; Dale, AM; Desikan, RS | Abstract: Background and purposeThe Entorhinal Cortex, a critical gateway between the neoCortex and hippocampus, is one of the earliest regions affected by Alzheimer disease-associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging-based measure of the Entorhinal Cortex, whether antemortem Entorhinal Cortex thickness is associated with postmortem tangle burden within the Entorhinal Cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of Entorhinal Cortex thickness and postmortem neuropathological measures.Materials and methodsWe evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the Entorhinal Cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between Entorhinal Cortex thickness and tangles and amyloid-β load within the Entorhinal Cortex and medial temporal and neocortical regions.ResultsWe found a significant relationship between antemortem Entorhinal Cortex thickness and Entorhinal Cortex (P = .006) and medial temporal lobe tangles (P = .002); we found no relationship between Entorhinal Cortex thickness and Entorhinal Cortex (P = .09) and medial temporal lobe amyloid-β (P = .09). We also found a significant association between Entorhinal Cortex thickness and cortical tangles (P = .003) and amyloid-β (P = .01). We found no relationship between parahippocampal gyrus thickness and Entorhinal Cortex (P = .31) and medial temporal lobe tangles (P = .051).ConclusionsOur findings indicate that Entorhinal Cortex-associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology.
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mri measures of Entorhinal Cortex vs hippocampus in preclinical ad
Neurology, 2002Co-Authors: Ronald J Killiany, Bradley T Hyman, Teresa Gomezisla, Mark B Moss, Ron Kikinis, Ferenc A Jolesz, Rudolph E Tanzi, Kenneth J Jones, Marilyn S AlbertAbstract:Background: MRI measures of the Entorhinal Cortex and the hippocampus have been used to predict which nondemented individuals with memory problems will progress to meet criteria for AD on follow-up, but their relative accuracy remains controversial. Objectives: To compare MRI measures of the Entorhinal Cortex and the hippocampus for predicting who will develop AD. Methods: MRI volumes of the Entorhinal Cortex and the hippocampus were obtained in 137 individuals comprising four groups: 1) individuals with normal cognition both at baseline and after 3 years of follow-up (n = 28), 2) subjects with memory difficulty but not dementia both at baseline and after 3 years of follow-up (n = 73), 3) subjects with memory difficulty at baseline who were diagnosed with probable AD within 3 years of follow-up (n = 21), and 4) patients with mild AD at baseline (n = 16). Results: Measures of both the Entorhinal Cortex and the hippocampus were different for each of the pairwise comparisons between the groups ( p p Conclusion: These findings are consistent with neuropathologic data showing substantial involvement of the Entorhinal Cortex in the preclinical phase of AD and suggest that, as the disease spreads, atrophic change develops within the hippocampus, which is measurable on MRI.
Menno P. Witter - One of the best experts on this subject based on the ideXlab platform.
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inhibitory connectivity dominates the fan cell network in layer ii of lateral Entorhinal Cortex
The Journal of Neuroscience, 2018Co-Authors: Eirik Stamland Nilssen, Bente Jacobsen, Gunhild Fjeld, Rajeevkumar R Nair, Stefan Blankvoort, Clifford G Kentros, Menno P. WitterAbstract:Fan cells in layer II of the lateral Entorhinal Cortex (LEC) form a main component of the projection to the dentate gyrus, CA3 and CA2 of the hippocampal formation. This projection has a counterpart originating from stellate cells in layer II of the medial Entorhinal Cortex (MEC). Available evidence suggests that the two pathways carry different information, exemplified by a difference in spatial tuning of cells in LEC and MEC. The grid cell, a prominent position-modulated cell type present in MEC, has been postulated to derive its characteristic hexagonal firing pattern from dominant disynaptic inhibitory connections between hippocampal-projecting stellate cells. Given that grid cells have not been described in LEC, we aim to describe the local synaptic connectivity of fan cells, to explore whether the network architecture is similar to that of the MEC stellate cell. Using a combination of in vitro multicell electrophysiological and optogenetic approaches in acute slices from rodents of either sex, we show that excitatory connectivity between fan cells is very sparse. Fan cells connect preferentially with two distinct types of inhibitory interneurons, suggesting disynaptic inhibitory coupling as the main form of communication among fan cells. These principles are similar to those reported for stellate cells in MEC, indicating an overall comparable local circuit architecture of the main hippocampal-projecting cell types in the lateral and medial Entorhinal Cortex. SIGNIFICANCE STATEMENT Our data provide the first description of the synaptic microcircuit of hippocampal-projecting layer II cells in the lateral Entorhinal Cortex. We show that these cells make infrequent monosynaptic connections with each other, and that they preferentially communicate through a disynaptic inhibitory network. This is similar to the microcircuit of hippocampal-projecting stellate cells in layer II of the medial Entorhinal Cortex, but dissimilar to the connectivity observed in layer 2 of neoCortex. In medial Entorhinal Cortex, the observed network structure has been proposed to underlie the firing pattern of grid cells. This opens the possibility that layer II cells in lateral Entorhinal Cortex exhibit regular firing patterns in an unexplored domain.
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Excitatory Postrhinal Projections to Principal Cells in the Medial Entorhinal Cortex.
Journal of Neuroscience, 2015Co-Authors: Noriko Koganezawa, Ragnhild Gisetstad, Ellen Husby, Thanh P. Doan, Menno P. WitterAbstract:The postrhinal Cortex (POR) provides substantial input to the Entorhinal Cortex, mainly targeting superficial layers of the medial Entorhinal Cortex (MEC). Major inputs to POR originate in the visual and parietal Cortex, thus providing neurons in MEC with a subset of cortical information relevant to their spatial firing properties. The POR takes a position that is comparable with that of the perirhinal Cortex (PER) with regard to the lateral Entorhinal Cortex (LEC). Neurons in LEC and MEC show different functional properties likely reflecting differences in their respective inputs. Projections from PER to LEC exert a main inhibitory influence, which may relate to the sparse object-selective firing in LEC. In view of the continuous, spatially modulated firing properties of principal neurons in MEC, we tested in rats the hypothesis that projections from POR to MEC are functionally different from the PER-to-LEC counterpart in providing an excitatory drive to MEC. Our combined confocal and quantitative electron-microscopic observations indicated that POR projections target mainly principal cells in MEC, including neurons that project to the hippocampus. The ultrastructure of the majority of the synapses indicated that they are excitatory. Voltage-sensitive dye imaging in sagittal slices confirmed this morphologically derived conclusion, showing that the MEC network always responded with an overall depolarization, indicative for net excitatory transmission. In vitro single-cell recordings from principal cells showed only excitatory responses upon POR stimulation. These results show that POR provides an excitatory projection to MEC, differing fundamentally from the inhibitory projection of PER to LEC.
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what does the anatomical organization of the Entorhinal Cortex tell us
Neural Plasticity, 2008Co-Authors: Cathrin B. Canto, Floris G. Wouterlood, Menno P. WitterAbstract:The Entorhinal Cortex is commonly perceived as a major input and output structure of the hippocampal formation, entertaining the role of the nodal point of cortico-hippocampal circuits. Superficial layers receive convergent cortical information, which is relayed to structures in the hippocampus, and hippocampal output reaches deep layers of Entorhinal Cortex, that project back to the Cortex. The finding of the grid cells in all layers and reports on interactions between deep and superficial layers indicate that this rather simplistic perception may be at fault. Therefore, an integrative approach on the Entorhinal Cortex, that takes into account recent additions to our knowledge database on Entorhinal connectivity, is timely. We argue that layers in Entorhinal Cortex show different functional characteristics most likely not on the basis of strikingly different inputs or outputs, but much more likely on the basis of differences in intrinsic organization, combined with very specific sets of inputs. Here, we aim to summarize recent anatomical data supporting the notion that the traditional description of the Entorhinal Cortex as a layered input-output structure for the hippocampal formation does not give the deserved credit to what this structure might be contributing to the overall functions of cortico-hippocampal networks.
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Progressive increase in grid scale from dorsal to ventral medial Entorhinal Cortex
Hippocampus, 2008Co-Authors: Vegard Heimly Brun, Kirsten Brun Kjelstrup, Trygve Solstad, Marianne Fyhn, Menno P. Witter, Edvard I. MoserAbstract:Grid cells are topographically organized in the sense that, within the dorsal part of the medial Entorhinal Cortex, the scale of the grid increases systematically with anatomical distance from the dorsal border of this brain area. The ventral limit of the spatial map is currently not known. To determine if the grid map extends into the intermediate and ventral parts of the medial Entorhinal Cortex, we recorded activity from Entorhinal principal cells at multiple dorsoventral levels while rats shuttled back and forth on an 18 m long linear track. The recordings spanned a range of more than 3 mm, covering approximately three quarters of the dorsoventral extent of the medial Entorhinal Cortex. Distinct periodic firing fields were observed at all recording levels. The average interpeak distance between the fields increased from approximately 50 cm in the most dorsal part to approximately 3 m at the most ventral recording positions. The increase in grid scale was accompanied by a decrease in the frequency of theta modulation and the rate of phase precession. The increase in average spacing and field size was approximately linear but this relationship coincided with a substantial increase in the variability of each measure. Taken together, the observations suggest that the spatial scale of the grid representation increases progressively along most of the dorsoventral axis of the medial Entorhinal Cortex, mirroring the topographical scale expansion observed in place cells in the hippocampus.
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Progressive increase in grid scale from dorsal to ventral medial Entorhinal Cortex
Hippocampus, 2008Co-Authors: Vegard Heimly Brun, Kirsten Brun Kjelstrup, Trygve Solstad, Marianne Fyhn, Edvard I. Moser, Menno P. Witter, Maybritt MoserAbstract:Grid cells are topographically organized in the sense that, within the dorsal part of the medial Entorhinal Cortex, the scale of the grid increases systematically with anatomical distance from the dor- sal border of this brain area. The ventral limit of the spatial map is cur- rently not known. To determine if the grid map extends into the inter- mediate and ventral parts of the medial Entorhinal Cortex, we recorded activity from Entorhinal principal cells at multiple dorsoventral levels while rats shuttled back and forth on an 18 m long linear track. The recordings spanned a range of more than 3 mm, covering approximately three quarters of the dorsoventral extent of the medial Entorhinal cor- tex. Distinct periodic firing fields were observed at all recording levels. The average interpeak distance between the fields increased from � 50 cm in the most dorsal part to � 3 m at the most ventral recording posi- tions. The increase in grid scale was accompanied by a decrease in the frequency of theta modulation and the rate of phase precession. The increase in average spacing and field size was approximately linear but this relationship coincided with a substantial increase in the variability of each measure. Taken together, the observations suggest that the spa- tial scale of the grid representation increases progressively along most of the dorsoventral axis of the medial Entorhinal Cortex, mirroring the topographical scale expansion observed in place cells in the hippocam- pus. V C 2008 Wiley-Liss, Inc.
David A Bennett - One of the best experts on this subject based on the ideXlab platform.
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Entorhinal Cortex antemortem cortical thickness and postmortem neurofibrillary tangles and amyloid pathology
American Journal of Neuroradiology, 2017Co-Authors: Ashesh A Thaker, Brent D Weinberg, William P Dillon, Christopher P Hess, Howard Cabral, Debra A Fleischman, Sue Leurgans, David A Bennett, Bradley T Hyman, Marilyn S AlbertAbstract:Author(s): Thaker, AA; Weinberg, BD; Dillon, WP; Hess, CP; Cabral, HJ; Fleischman, DA; Leurgans, SE; Bennett, DA; Hyman, BT; Albert, MS; Killiany, RJ; Fischl, B; Dale, AM; Desikan, RS | Abstract: The Entorhinal Cortex, a critical gateway between the neoCortex and hippocampus, is one of the earliest regions affected by Alzheimer disease-associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging-based measure of the Entorhinal Cortex, whether antemortem Entorhinal Cortex thickness is associated with postmortem tangle burden within the Entorhinal Cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of Entorhinal Cortex thickness and postmortem neuropathological measures.We evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the Entorhinal Cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between Entorhinal Cortex thickness and tangles and amyloid-β load within the Entorhinal Cortex and medial temporal and neocortical regions.We found a significant relationship between antemortem Entorhinal Cortex thickness and Entorhinal Cortex (P = .006) and medial temporal lobe tangles (P = .002); we found no relationship between Entorhinal Cortex thickness and Entorhinal Cortex (P = .09) and medial temporal lobe amyloid-β (P = .09). We also found a significant association between Entorhinal Cortex thickness and cortical tangles (P = .003) and amyloid-β (P = .01). We found no relationship between parahippocampal gyrus thickness and Entorhinal Cortex (P = .31) and medial temporal lobe tangles (P = .051).Our findings indicate that Entorhinal Cortex-associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology.
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Entorhinal Cortex antemortem cortical thickness and postmortem neurofibrillary tangles and amyloid pathology
American Journal of Neuroradiology, 2017Co-Authors: Ashesh A Thaker, Brent D Weinberg, William P Dillon, Christopher P Hess, Howard Cabral, Debra A Fleischman, Sue Leurgans, David A Bennett, Bradley T Hyman, Marilyn S AlbertAbstract:BACKGROUND AND PURPOSE: The Entorhinal Cortex, a critical gateway between the neoCortex and hippocampus, is one of the earliest regions affected by Alzheimer disease–associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging–based measure of the Entorhinal Cortex, whether antemortem Entorhinal Cortex thickness is associated with postmortem tangle burden within the Entorhinal Cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of Entorhinal Cortex thickness and postmortem neuropathological measures. MATERIALS AND METHODS: We evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the Entorhinal Cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between Entorhinal Cortex thickness and tangles and amyloid-β load within the Entorhinal Cortex and medial temporal and neocortical regions. RESULTS: We found a significant relationship between antemortem Entorhinal Cortex thickness and Entorhinal Cortex (P = .006) and medial temporal lobe tangles (P = .002); we found no relationship between Entorhinal Cortex thickness and Entorhinal Cortex (P = .09) and medial temporal lobe amyloid-β (P = .09). We also found a significant association between Entorhinal Cortex thickness and cortical tangles (P = .003) and amyloid-β (P = .01). We found no relationship between parahippocampal gyrus thickness and Entorhinal Cortex (P = .31) and medial temporal lobe tangles (P = .051). CONCLUSIONS: Our findings indicate that Entorhinal Cortex–associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology.
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Entorhinal Cortex antemortem cortical thickness and postmortem neurofibrillary tangles and amyloid pathology
American Journal of Neuroradiology, 2017Co-Authors: Ashesh A Thaker, Brent D Weinberg, William P Dillon, Christopher P Hess, Howard Cabral, Debra A Fleischman, Sue Leurgans, David A Bennett, Bradley T Hyman, Marilyn S AlbertAbstract:Author(s): Thaker, AA; Weinberg, BD; Dillon, WP; Hess, CP; Cabral, HJ; Fleischman, DA; Leurgans, SE; Bennett, DA; Hyman, BT; Albert, MS; Killiany, RJ; Fischl, B; Dale, AM; Desikan, RS | Abstract: Background and purposeThe Entorhinal Cortex, a critical gateway between the neoCortex and hippocampus, is one of the earliest regions affected by Alzheimer disease-associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging-based measure of the Entorhinal Cortex, whether antemortem Entorhinal Cortex thickness is associated with postmortem tangle burden within the Entorhinal Cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of Entorhinal Cortex thickness and postmortem neuropathological measures.Materials and methodsWe evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the Entorhinal Cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between Entorhinal Cortex thickness and tangles and amyloid-β load within the Entorhinal Cortex and medial temporal and neocortical regions.ResultsWe found a significant relationship between antemortem Entorhinal Cortex thickness and Entorhinal Cortex (P = .006) and medial temporal lobe tangles (P = .002); we found no relationship between Entorhinal Cortex thickness and Entorhinal Cortex (P = .09) and medial temporal lobe amyloid-β (P = .09). We also found a significant association between Entorhinal Cortex thickness and cortical tangles (P = .003) and amyloid-β (P = .01). We found no relationship between parahippocampal gyrus thickness and Entorhinal Cortex (P = .31) and medial temporal lobe tangles (P = .051).ConclusionsOur findings indicate that Entorhinal Cortex-associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology.
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loss and atrophy of layer ii Entorhinal Cortex neurons in elderly people with mild cognitive impairment
Annals of Neurology, 2001Co-Authors: Jeffrey H Kordower, David A Bennett, Glenn T Stebbins, Steven T Dekosky, Elizabeth J Cochran, Elliott J MufsonAbstract:Layer II of the Entorhinal Cortex contains the cells of origin for the perforant path, plays a critical role in memory processing, and consistently degenerates in end-stage Alzheimer's disease. The extent to which neuron loss in layer II of Entorhinal Cortex is related to mild cognitive impairment without dementia has not been extensively investigated. We analyzed 29 participants who came to autopsy from our ongoing longitudinal study of aging and dementia composed of religious clergy (Religious Orders Study). All individuals underwent detailed clinical evaluation within 12 months of death and were categorized as having no cognitive impairment (n = 8), mild cognitive impairment (n = 10), or mild or moderate Alzheimer's disease (n = 11). Sections through the Entorhinal Cortex were immunoreacted with an antibody directed against a neuron-specific nuclear protein (NeuN). Stereological counts of NeuN-immunoreactive stellate cells, their volume, and the volume of layer II Entorhinal Cortex were estimated. Cases exhibiting no cognitive impairment averaged 639,625 ± 184,600 layer II stellate neurons in the right Entorhinal Cortex. Individuals with mild cognitive impairment (63.5%; p 0.33). There was also significant atrophy of layer II Entorhinal Cortex neurons in individuals with mild cognitive impairment (24.1%) and Alzheimer's disease (25.1%). The volume of layer II was also reduced in individuals with mild cognitive impairment (26.5%), with a further reduction in those with Alzheimer's disease (46.4%). The loss and atrophy of layer II Entorhinal Cortex neurons significantly correlated with performance on clinical tests of declarative memory. Atrophy of layer II Entorhinal Cortex and the neurons within this layer significantly correlated with performance on the Mini Mental Status Examination. These data indicate that atrophy and loss of layer II Entorhinal Cortex neurons occur in elderly subjects with mild cognitive impairment prior to the onset of dementia and suggests that these changes are not exacerbated in early Alzheimer's disease. Ann Neurol 2001;49:202–213
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loss and atrophy of layer ii Entorhinal Cortex neurons in elderly people with mild cognitive impairment
Annals of Neurology, 2001Co-Authors: Jeffrey H Kordower, David A Bennett, Glenn T Stebbins, Steven T Dekosky, Elizabeth J Cochran, Yaping Chu, Elliott J MufsonAbstract:Layer II of the Entorhinal Cortex contains the cells of origin for the perforant path, plays a critical role in memory processing, and consistently degenerates in end-stage Alzheimer's disease. The extent to which neuron loss in layer II of Entorhinal Cortex is related to mild cognitive impairment without dementia has not been extensively investigated. We analyzed 29 participants who came to autopsy from our ongoing longitudinal study of aging and dementia composed of religious clergy (Religious Orders Study). All individuals underwent detailed clinical evaluation within 12 months of death and were categorized as having no cognitive impairment (n = 8), mild cognitive impairment (n = 10), or mild or moderate Alzheimer's disease (n = 11). Sections through the Entorhinal Cortex were immunoreacted with an antibody directed against a neuron-specific nuclear protein (NeuN). Stereological counts of NeuN-immunoreactive stellate cells, their volume, and the volume of layer II Entorhinal Cortex were estimated. Cases exhibiting no cognitive impairment averaged 639,625 +/- 184,600 layer II stellate neurons in the right Entorhinal Cortex. Individuals with mild cognitive impairment (63.5%; p 0.33). There was also significant atrophy of layer II Entorhinal Cortex neurons in individuals with mild cognitive impairment (24.1%) and Alzheimer's disease (25.1%). The volume of layer II was also reduced in individuals with mild cognitive impairment (26.5%), with a further reduction in those with Alzheimer's disease (46.4%). The loss and atrophy of layer II Entorhinal Cortex neurons significantly correlated with performance on clinical tests of declarative memory. Atrophy of layer II Entorhinal Cortex and the neurons within this layer significantly correlated with performance on the Mini Mental Status Examination. These data indicate that atrophy and loss of layer II Entorhinal Cortex neurons occur in elderly subjects with mild cognitive impairment prior to the onset of dementia and suggests that these changes are not exacerbated in early Alzheimer's disease.
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Object-vector coding in the medial Entorhinal Cortex
Nature, 2019Co-Authors: Oyvind Arne Hoydal, Emilie Ranheim Skytoen, Maybritt Moser, Sebastian Ola Andersson, Edvard I. MoserAbstract:The hippocampus and the medial Entorhinal Cortex are part of a brain system that maps self-location during navigation in the proximal environment1,2. 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 cells3, grid cells4, border cells5,6 and head-direction cells7. 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 navigation8–10. Theoretical studies have proposed that such vector operations are supported by neurons that use distance and direction from discrete objects11,12 or boundaries13,14 to determine the animal’s location, but—although some cells with vector-coding properties may be present in the hippocampus15 and subiculum16,17—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. Cells in the mouse medial Entorhinal Cortex that fire when mice are at a specific distance and direction from a stationary object suggest that vector coding is important for rodent navigation.
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integrating time from experience in the lateral Entorhinal Cortex
Nature, 2018Co-Authors: Albert Tsao, Maybritt Moser, Jorgen Sugar, Cheng Wang, James J Knierim, Edvard I. MoserAbstract: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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speed cells in the medial Entorhinal Cortex
Nature, 2015Co-Authors: Emilio Kropff, Maybritt Moser, James E. Carmichael, Edvard I. MoserAbstract: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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Speed cells in the medial Entorhinal Cortex
Nature, 2015Co-Authors: Emilio Kropff, Maybritt Moser, James E. Carmichael, Edvard I. MoserAbstract: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. On the basis of neural firing rates a specific class of neuron is identified in the medial Entorhinal Cortex that linearly encodes information on running speed in a context-independent manner and that is distinct from other functionally specific Entorhinal neurons. It has long been postulated that in the Entorhinal Cortex, grid cells require information on the running speed of the animal in order to properly encode periodic spatial firing fields as an animal moves through its environment. However, the source of such a signal transmitting speed information has not been previously identified. Here, Edvard Moser and colleagues isolate a specific class of neurons in the medial Entorhinal Cortex (MEC) that encode information linearly on running speed based on neural firing rates. These 'speed cells' are distinct from other functionally specific MEC neurons and encode speed in a context-independent manner.
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traces of experience in the lateral Entorhinal Cortex
Current Biology, 2013Co-Authors: Albert Tsao, Maybritt Moser, Edvard I. MoserAbstract:Summary A growing body of evidence suggests that memories are stored in the hippocampus by integrating spatial information from specialized cell types in the medial Entorhinal Cortex (MEC) with nonspatial information from cells in the lateral Entorhinal Cortex (LEC) [1–5]. LEC neurons show little spatial modulation when rats run in empty open-field environments [6, 7] but fire in the vicinity of discrete objects [7], suggesting that they provide information about the specific content of the spatial environment. It is unclear, however, whether firing at objects is elicited purely by stimulus properties, in a sensory-like manner, or whether any higher-order property, such as the history of experience, is also relevant. To address this question, we recorded from LEC neurons in an open field where objects were present on a subset of the trials. Whereas some neurons fired at the objects, other cells developed specific firing at places where objects had been located on previous trials, providing a readout of past experience in the environment. The latter cells generally did not respond to the object when it was present, suggesting that object cells and object-trace cells are independent cell classes. These findings identify LEC as a component of the hippocampal-cortical circuit for object-place memory.