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Michael E Hasselmo - One of the best experts on this subject based on the ideXlab platform.
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rebound spiking in layer ii medial entorhinal cortex stellate Cells possible mechanism of Grid Cell function
Neurobiology of Learning and Memory, 2016Co-Authors: Christopher F Shay, Michele Ferrante, William G Chapman, Michael E HasselmoAbstract:Rebound spiking properties of medial entorhinal cortex (mEC) stellate Cells induced by inhibition may underlie their functional properties in awake behaving rats, including the temporal phase separation of distinct Grid Cells and differences in Grid Cell firing properties. We investigated rebound spiking properties using whole Cell patch recording in entorhinal slices, holding Cells near spiking threshold and delivering sinusoidal inputs, superimposed with realistic inhibitory synaptic inputs to test the capacity of Cells to selectively respond to specific phases of inhibitory input. Stellate Cells showed a specific phase range of hyperpolarizing inputs that elicited spiking, but non-stellate Cells did not show phase specificity. In both Cell types, the phase range of spiking output occurred between the peak and subsequent descending zero crossing of the sinusoid. The phases of inhibitory inputs that induced spikes shifted earlier as the baseline sinusoid frequency increased, while spiking output shifted to later phases. Increases in magnitude of the inhibitory inputs shifted the spiking output to earlier phases. Pharmacological blockade of h-current abolished the phase selectivity of hyperpolarizing inputs eliciting spikes. A network computational model using Cells possessing similar rebound properties as found in vitro produces spatially periodic firing properties resembling Grid Cell firing when a simulated animal moves along a linear track. These results suggest that the ability of mEC stellate Cells to fire rebound spikes in response to a specific range of phases of inhibition could support complex attractor dynamics that provide completion and separation to maintain spiking activity of specific Grid Cell populations.
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Grid Cell spatial tuning reduced following systemic muscarinic receptor blockade
Hippocampus, 2014Co-Authors: Ehren L. Newman, Jason R. Climer, Michael E HasselmoAbstract:Grid Cells of the medial entorhinal cortex exhibit a periodic and stable pattern of spatial tuning that may reflect the output of a path integration system. This Grid pattern has been hypothesized to serve as a spatial coordinate system for navigation and memory function. The mechanisms underlying the generation of this characteristic tuning pattern remain poorly understood. Systemic administration of the muscarinic antagonist scopolamine flattens the typically positive correlation between running speed and entorhinal theta frequency in rats. The loss of this neural correlate of velocity, an important signal for the calculation of path integration, raises the question of what influence scopolamine has on the Grid Cell tuning as a read out of the path integration system. To test this, the spatial tuning properties of Grid Cells were compared before and after systemic administration of scopolamine as rats completed laps on a circle track for food rewards. The results show that the spatial tuning of the Grid Cells was reduced following scopolamine administration. The tuning of head direction Cells, in contrast, was not reduced by scopolamine. This is the first report to demonstrate a link between cholinergic function and Grid Cell tuning. This work suggests that the loss of tuning in the Grid Cell network may underlie the navigational disorientation observed in Alzheimer's patients and elderly individuals with reduced cholinergic tone.
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dc shifts in amplitude in field generated by an oscillatory interference model of Grid Cell firing
Frontiers in Systems Neuroscience, 2014Co-Authors: Angela C E Onslow, Michael E Hasselmo, Ehren L. NewmanAbstract:Oscillatory interference models propose a mechanism by which the spatial firing pattern of Grid Cells can arise from the interaction of multiple oscillators that shift in relative phase. These models produce aspects of the physiological data such as the phase precession dynamics observed in Grid Cells. However, existing oscillatory interference models did not predict the in-field DC shifts in the membrane potential of Grid Cells that have been observed during intraCellular recordings in navigating animals. Here, we demonstrate that DC shifts can be generated in an oscillatory interference model when half-wave rectified oscillatory inputs are summed by a leaky integrate-and-fire neuron with a long membrane decay constant (100 ms). The nonlinear mean of the half-wave rectified input signal is reproduced in the Grid Cell’s membrane potential trace producing the DC shift within field. For shorter values of the decay constant integration is more effective if the input signal, comprising input from 6 head direction selective populations, is temporally spread during in-field epochs; this requires that the head direction selective populations act as velocity controlled oscillators with baseline oscillations that are phase offset from one another. The resulting simulated membrane potential matches several properties of the empirical intraCellular recordings, including: in-field DC-shifts, theta-band oscillations, phase precession of both membrane potential oscillations and Grid Cell spiking activity relative to network theta and a stronger correlation between DC-shift amplitude and firing-rate than between theta-band oscillation amplitude and firing-rate. This work serves to demonstrate that oscillatory interference models can account for the DC shifts in the membrane potential observed during intraCellular recordings of Grid Cells without the need to appeal to attractor dynamics.
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comparison of properties of medial entorhinal cortex layer ii neurons in two anatomical dimensions with and without cholinergic activation
PLOS ONE, 2013Co-Authors: Arthur Jochems, Motoharu Yoshida, Michael E HasselmoAbstract:Mechanisms underlying Grid Cell firing in the medial entorhinal cortex (MEC) still remain unknown. Computational modeling studies have suggested that Cellular properties such as spike frequency adaptation and persistent firing might underlie the Grid Cell firing. Recent in vivo studies also suggest that cholinergic activation influences Grid Cell firing. Here we investigated the anatomical distribution of firing frequency adaptation, the medium spike after hyperpolarization potential (mAHP), subthreshold membrane potential oscillations, sag potential, input resistance and persistent firing, in MEC layer II principal Cells using in vitro whole-Cell patch clamp recordings in rats. Anatomical distributions of these properties were compared along both the dorso-ventral and medio-lateral axes, both with and without the cholinergic receptor agonist carbachol. We found that spike frequency adaptation is significantly stronger in ventral than in dorsal neurons both with and without carbachol. Spike frequency adaptation was significantly correlated with the duration of the mAHP, which also showed a gradient along the dorso-ventral axis. In carbachol, we found that about 50% of MEC layer II neurons show persistent firing which lasted more than 30 seconds. Persistent firing of MEC layer II neurons might contribute to Grid Cell firing by providing the excitatory drive. Dorso-ventral differences in spike frequency adaptation we report here are opposite from previous predictions by a computational model. We discuss an alternative mechanism as to how dorso-ventral differences in spike frequency adaptation could contribute to different scales of Grid spacing.
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A model combining oscillations and attractor dynamics for generation of Grid Cell firing.
Frontiers in Neural Circuits, 2012Co-Authors: Michael E Hasselmo, Mark P BrandonAbstract:Different models have been able to account for different features of the data on Grid Cell firing properties, including the relationship of Grid Cells to Cellular properties and network oscillations. This paper describes a model that combines elements of two major classes of models of Grid Cells: models using interference of oscillations and models using attractor dynamics. This model includes a population of units with oscillatory input representing input from the medial septum. These units are termed heading angle Cells because their connectivity depends upon heading angle in the environment as well as the spatial phase coded by the Cell. These Cells project to a population of Grid Cells. The sum of the heading angle input results in standing waves of circularly symmetric input to the Grid Cell population. Feedback from the Grid Cell population increases the activity of subsets of the heading angle Cells, resulting in the network settling into activity patterns that resemble the patterns of firing fields in a population of Grid Cells. The properties of heading angle Cells firing as conjunctive Grid-by-head-direction Cells can shift the Grid Cell firing according to movement velocity. The pattern of interaction of oscillations requires use of separate populations that fire on alternate cycles of the net theta rhythmic input to Grid Cells, similar to recent neurophysiological data on theta cycle skipping in medial entorhinal cortex.
John Okeefe - One of the best experts on this subject based on the ideXlab platform.
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Grid Cell symmetry is shaped by environmental geometry
Nature, 2015Co-Authors: Julija Krupic, Caswell Barry, Marius Bauza, Stephen Burton, John OkeefeAbstract:The neuronal Grid Cells of the entorhinal cortex fire in a spatial Grid pattern laid out across the surface of a familiar environment to provide the brain with an internal map of an animal's surroundings. The role of environmental boundaries in the construction of this pattern is not well understood. Early studies had suggested that properties such as symmetry, orientation and scale of Grid Cells' firing patterns were independent of an environment's shape. But now two separate papers in this issue of Nature one from Edvard Moser and colleagues and the other from John O'Keefe and colleagues demonstrate that Grid orientation, scale, symmetry and homogeneity can be strongly affected by environmental geometry, with Grid Cells aligned with the borders of the environment at an offset of a few degrees such that it minimizes symmetry with boundaries. These findings suggest a mechanism by which the geometry of an environment causes local rotation and deformation of the hexagonal firing patterns of Grid Cells.
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how environment geometry affects Grid Cell symmetry and what we can learn from it
Philosophical Transactions of the Royal Society B, 2014Co-Authors: Julija Krupic, Marius Bauza, Stephen Burton, Colin Lever, John OkeefeAbstract:The mammalian hippocampal formation provides neuronal representations of environmental location but the underlying mechanisms are unclear. The majority of Cells in medial entorhinal cortex and parasubiculum show spatially periodic firing patterns. Grid Cells exhibit hexagonal symmetry and form an important subset of this more general class. Occasional changes between hexagonal and non-hexagonal firing patterns imply a common underlying mechanism. Importantly, the symmetrical properties are strongly affected by the geometry of the environment. Here, we introduce a field–boundary interaction model where we demonstrate that the Grid Cell pattern can be formed from competing place-like and boundary inputs. We show that the modelling results can accurately capture our current experimental observations.
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models of place and Grid Cell firing and theta rhythmicity
Current Opinion in Neurobiology, 2011Co-Authors: Neil Burgess, John OkeefeAbstract:Neuronal firing in the hippocampal formation (HF) of freely moving rodents shows striking examples of spatialorganization in the form of place, directional, boundary vector and Grid Cells. The firing of place and Grid Cells shows an intriguing form of temporal organization known as ‘theta phase precession’. We review the mechanisms underlying theta phase precession of place Cell firing, ranging from membrane potential oscillations to recurrent connectivity, and the relevant intra-Cellular and extra-Cellular data. We then consider the use of these models to explain the spatial structure of Grid Cell firing, and review the relevant intra-Cellular and extra-Cellular data. Finally, we consider the likely interaction between place Cells, Grid Cells and boundary vector Cells in estimating self-location as a compromise between path-integration and environmental information.
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an oscillatory interference model of Grid Cell firing
Hippocampus, 2007Co-Authors: Neil Burgess, Caswell Barry, John OkeefeAbstract:We expand upon our proposal that the oscillatory inter- ference mechanism proposed for the phase precession effect in place Cells underlies the Grid-like firing pattern of dorsomedial entorhinal Grid Cells (O'Keefe and Burgess (2005) Hippocampus 15:853-866). The origi- nal one-dimensional interference model is generalized to an appropriate two-dimensional mechanism. Specifically, dendritic subunits of layer II medial entorhinal stellate Cells provide multiple linear interference patterns along different directions, with their product determining the firing of the Cell. Connection of appropriate speed- and direction- de- pendent inputs onto dendritic subunits could result from an unsuper- vised learning rule which maximizes postsynaptic firing (e.g. competi- tive learning). These inputs cause the intrinsic oscillation of subunit membrane potential to increase above theta frequency by an amount proportional to the animal's speed of running in the ''preferred'' direc- tion. The phase difference between this oscillation and a somatic input at theta-frequency essentially integrates velocity so that the interference of the two oscillations reflects distance traveled in the preferred direc- tion. The overall Grid pattern is maintained in environmental location by phase reset of the Grid Cell by place Cells receiving sensory input from the environment, and environmental boundaries in particular. We also outline possible variations on the basic model, including the generation of Grid-like firing via the interaction of multiple Cells rather than via multiple dendritic subunits. Predictions of the interference model are given for the frequency composition of EEG power spectra and temporal autocorrelograms of Grid Cell firing as functions of the speed and direc- tion of running and the novelty of the environment. V C 2007 Wiley-Liss, Inc.
Christian F Doeller - One of the best experts on this subject based on the ideXlab platform.
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Deforming the metric of cognitive maps distorts memory
Nature Human Behaviour, 2020Co-Authors: Jacob L S Bellmund, Caswell Barry, William De Cothi, Tom A. Ruiter, Christian F DoellerAbstract:Environmental boundaries anchor cognitive maps that support memory. However, trapezoidal boundary geometry distorts the regular firing patterns of entorhinal Grid Cells, proposedly providing a metric for cognitive maps. Here we test the impact of trapezoidal boundary geometry on human spatial memory using immersive virtual reality. Consistent with reduced regularity of Grid patterns in rodents and a Grid-Cell model based on the eigenvectors of the successor representation, human positional memory was degraded in a trapezoid environment compared with a square environment—an effect that was particularly pronounced in the narrow part of the trapezoid. Congruent with changes in the spatial frequency of eigenvector Grid patterns, distance estimates between remembered positions were persistently biased, revealing distorted memory maps that explained behaviour better than the objective maps. Our findings demonstrate that environmental geometry affects human spatial memory in a similar manner to rodent Grid-Cell activity and, therefore, strengthen the putative link between Grid Cells and behaviour along with their cognitive functions beyond navigation. Bellmund et al. use immersive virtual reality combined with successor representation modelling to show that environmental geometry distorts human spatial memory consistent with deformations of Grid-Cell firing patterns in navigating rodents.
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Grid Cell representations in mental simulation
eLife, 2016Co-Authors: Lorena Deuker, Jacob L S Bellmund, Tobias Navarro Schroder, Christian F DoellerAbstract:Recordings of brain activity in moving rats have found neurons that fire when the rat is at specific locations. These neurons are known as Grid Cells because their activity produces a Grid-like pattern. A separate group of neurons, called head direction Cells, represents the rat’s facing direction. Functional magnetic resonance imaging (fMRI) studies that have tracked brain activity in humans as they navigate virtual environments have found similar Grid-like and direction-related responses. A recent study showed Grid-like responses even if the people being studied just imagined moving around an arena while lying still. Theoretical work suggests that spatially tuned Cells might generally be important for our ability to imagine and simulate future events. However, it is not clear whether these location- and direction-responsive Cells are active when people do not visualize themselves moving. Bellmund et al. used fMRI to track brain activity in volunteers as they imagined different views in a virtual reality city. Before the fMRI experiment, the volunteers completed extensive training where they learned the layout of the city and the names of its buildings. Then, during the fMRI experiment, the volunteers had to imagine themselves standing in front of certain buildings and facing different directions. Crucially, they did not imagine themselves moving between these buildings. By using representational similarity analysis, which compares patterns of brain activity, Bellmund et al. could distinguish between the directions the volunteers were imagining. Activity patterns in the parahippocampal gyrus (a brain region known to be important for navigation) were more similar when participants were imagining similar directions. The fMRI results also show Grid-like responses in a brain area called entorhinal cortex, which is known to contain Grid Cells. While participants were imagining, this region exhibited activity patterns with a six-fold symmetry, as Bellmund et al. predicted from the characteristic firing patterns of Grid Cells. The findings presented by Bellmund et al. provide evidence that suggests that Grid Cells are involved in planning how to navigate, and so support previous theoretical assumptions. The computations of these Cells might contribute to other kinds of thinking too, such as remembering the past or imagining future events.
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Grid-Cell representations in mental simulation
eLife, 2016Co-Authors: Jacob L S Bellmund, Lorena Deuker, Tobias Navarro Schroder, Christian F DoellerAbstract:Anticipating the future is a key motif of the brain, possibly supported by mental simulation of upcoming events. Rodent single-Cell recordings suggest the ability of spatially tuned Cells to represent subsequent locations. Grid-like representations have been observed in the human entorhinal cortex during virtual and imagined navigation. However, hitherto it remains unknown if Grid-like representations contribute to mental simulation in the absence of imagined movement. Participants imagined directions between building locations in a large-scale virtual-reality city while undergoing fMRI without re-exposure to the environment. Using multi-voxel pattern analysis, we provide evidence for representations of absolute imagined direction at a resolution of 30° in the parahippocampal gyrus, consistent with the head-direction system. Furthermore, we capitalize on the six-fold rotational symmetry of Grid-Cell firing to demonstrate a 60° periodic pattern-similarity structure in the entorhinal cortex. Our findings imply a role of the entorhinal Grid-system in mental simulation and future thinking beyond spatial navigation.
Jacob L S Bellmund - One of the best experts on this subject based on the ideXlab platform.
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Deforming the metric of cognitive maps distorts memory
Nature Human Behaviour, 2020Co-Authors: Jacob L S Bellmund, Caswell Barry, William De Cothi, Tom A. Ruiter, Christian F DoellerAbstract:Environmental boundaries anchor cognitive maps that support memory. However, trapezoidal boundary geometry distorts the regular firing patterns of entorhinal Grid Cells, proposedly providing a metric for cognitive maps. Here we test the impact of trapezoidal boundary geometry on human spatial memory using immersive virtual reality. Consistent with reduced regularity of Grid patterns in rodents and a Grid-Cell model based on the eigenvectors of the successor representation, human positional memory was degraded in a trapezoid environment compared with a square environment—an effect that was particularly pronounced in the narrow part of the trapezoid. Congruent with changes in the spatial frequency of eigenvector Grid patterns, distance estimates between remembered positions were persistently biased, revealing distorted memory maps that explained behaviour better than the objective maps. Our findings demonstrate that environmental geometry affects human spatial memory in a similar manner to rodent Grid-Cell activity and, therefore, strengthen the putative link between Grid Cells and behaviour along with their cognitive functions beyond navigation. Bellmund et al. use immersive virtual reality combined with successor representation modelling to show that environmental geometry distorts human spatial memory consistent with deformations of Grid-Cell firing patterns in navigating rodents.
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Electrophysiological markers of Grid Cell population activity across species
2018Co-Authors: T. Navarro Schröder, Jacob L S Bellmund, M. Morreaunet, T.j. Staudigl, J.b. Julian, J.m. Schoffelen, C.f.a. DöllerAbstract:Grid Cells in the rodent and human entorhinal cortex are a critical component of the brain’s spatial coding system. In virtual-reality (VR) navigation tasks in humans, the fMRI BOLD signal in the entorhinal cortex exhibits hexadirectional modulations that may reflect population activity of Grid Cells. However, it remains unknown whether and how Grid Cell population activity specifically gives rise to this hexadirectional hemodynamic fMRI signal. Here we address this issue in two steps. First, we employed a VR navigation experiment using magnetoencephalography (MEG) in human participants and found hexadirectional signal modulations in the high-gamma band, source-localised to the medial temporal lobe. Next, we conducted analyses to test the relationship between Grid Cell activity and local field potential (LFP) recordings in freely moving rats. We found hexadirectional modulations in the same frequency band as in the human MEG navigation experiment. The orientation of this hexadirectional LFP modulation was aligned to the orientation of the hexagonally symmetric firing patterns of Grid Cells. Together, these findings describe new ways to measure Grid Cell population activity and their non-invasive source localisation using MEG. Crucially, we link Grid Cell activity to measures of population activity in rats and humans, thereby elucidating the physiological basis of non-invasive Grid Cell population measures previously revealed with fMRI. Since Grid Cell function is affected early in Alzheimer ’s disease, understanding how to measure their activity with non-invasive methods is of high clinical relevance.
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Grid Cell representations in mental simulation
eLife, 2016Co-Authors: Lorena Deuker, Jacob L S Bellmund, Tobias Navarro Schroder, Christian F DoellerAbstract:Recordings of brain activity in moving rats have found neurons that fire when the rat is at specific locations. These neurons are known as Grid Cells because their activity produces a Grid-like pattern. A separate group of neurons, called head direction Cells, represents the rat’s facing direction. Functional magnetic resonance imaging (fMRI) studies that have tracked brain activity in humans as they navigate virtual environments have found similar Grid-like and direction-related responses. A recent study showed Grid-like responses even if the people being studied just imagined moving around an arena while lying still. Theoretical work suggests that spatially tuned Cells might generally be important for our ability to imagine and simulate future events. However, it is not clear whether these location- and direction-responsive Cells are active when people do not visualize themselves moving. Bellmund et al. used fMRI to track brain activity in volunteers as they imagined different views in a virtual reality city. Before the fMRI experiment, the volunteers completed extensive training where they learned the layout of the city and the names of its buildings. Then, during the fMRI experiment, the volunteers had to imagine themselves standing in front of certain buildings and facing different directions. Crucially, they did not imagine themselves moving between these buildings. By using representational similarity analysis, which compares patterns of brain activity, Bellmund et al. could distinguish between the directions the volunteers were imagining. Activity patterns in the parahippocampal gyrus (a brain region known to be important for navigation) were more similar when participants were imagining similar directions. The fMRI results also show Grid-like responses in a brain area called entorhinal cortex, which is known to contain Grid Cells. While participants were imagining, this region exhibited activity patterns with a six-fold symmetry, as Bellmund et al. predicted from the characteristic firing patterns of Grid Cells. The findings presented by Bellmund et al. provide evidence that suggests that Grid Cells are involved in planning how to navigate, and so support previous theoretical assumptions. The computations of these Cells might contribute to other kinds of thinking too, such as remembering the past or imagining future events.
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Grid-Cell representations in mental simulation
eLife, 2016Co-Authors: Jacob L S Bellmund, Lorena Deuker, Tobias Navarro Schroder, Christian F DoellerAbstract:Anticipating the future is a key motif of the brain, possibly supported by mental simulation of upcoming events. Rodent single-Cell recordings suggest the ability of spatially tuned Cells to represent subsequent locations. Grid-like representations have been observed in the human entorhinal cortex during virtual and imagined navigation. However, hitherto it remains unknown if Grid-like representations contribute to mental simulation in the absence of imagined movement. Participants imagined directions between building locations in a large-scale virtual-reality city while undergoing fMRI without re-exposure to the environment. Using multi-voxel pattern analysis, we provide evidence for representations of absolute imagined direction at a resolution of 30° in the parahippocampal gyrus, consistent with the head-direction system. Furthermore, we capitalize on the six-fold rotational symmetry of Grid-Cell firing to demonstrate a 60° periodic pattern-similarity structure in the entorhinal cortex. Our findings imply a role of the entorhinal Grid-system in mental simulation and future thinking beyond spatial navigation.
Michael Häusser - One of the best experts on this subject based on the ideXlab platform.
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How to build a Grid Cell
Philosophical Transactions of the Royal Society B: Biological Sciences, 2014Co-Authors: Christoph Schmidt-hieber, Michael HäusserAbstract:Neurons in the medial entorhinal cortex fire action potentials at regular spatial intervals, creating a striking Grid-like pattern of spike rates spanning the whole environment of a navigating animal. This remarkable spatial code may represent a neural map for path integration. Recent advances using patch-clamp recordings from entorhinal cortex neurons in vitro and in vivo have revealed how the microcircuitry in the medial entorhinal cortex may contribute to Grid Cell firing patterns, and how Grid Cells may transform synaptic inputs into spike output during firing field crossings. These new findings provide key insights into the ingredients necessary to build a Grid Cell.
