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Biomedical subjects

Edvard I Moser

Publications and source records attributed to Edvard I Moser.

At least 19 recordsLinked to original sources
PubMed2006

Spatial representation and the architecture of the entorhinal cortex.

It has recently been recognized that the entorhinal cortex has a crucial role in spatial representation and navigation. How the position of an animal is computed within the entorhinal circuitry remains to be determined, but the architectural organization of this brain area might provide some clues. Here, we review three organizational principles--recurrent connectivity, interlaminar connectivity and modular organization--and propose how each of them might contribute to the emergence and maintenance of positional representations in entorhinal neural networks.

Animals↗
PubMed2006

Conjunctive representation of position, direction, and velocity in entorhinal cortex.

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

Animals↗
PubMed2006

Fast rate coding in hippocampal CA3 cell ensembles.

Environments with overlapping features are represented by distinct patterns of activity in the hippocampus, enabling information to be stored and retrieved with minimal interference. This orthogonalization of correlated inputs is thought to take place within the hippocampus itself. However, the orthogonalization process has been shown to take days to develop in CA1. This prolonged time course is in striking contrast to the fast encoding of behavioral memory by the hippocampus. To explore this apparent paradox, we asked whether orthogonalization depended on the type of remapping exhibited by the hippocampal network. We have previously distinguished two types of remapping, global remapping, which results in the activation of different assemblies of place fields, and rate remapping, which encodes differences between cue constellations by substantial changes in firing rate without a change in the place code. Global remapping has previously been shown to be expressed immediately at novel locations. Here we asked if rate remapping follows a slower time course. Ensemble activity was recorded simultaneously from CA3 and CA1 in rats exposed to two similar, novel environments. It was found that rate changes in response to novel sensory cue configurations can form immediately, just as during global remapping, in particular in CA3. The fast encoding of both spatial and nonspatial information in CA3 is consistent with a role for the autoassociative CA3 circuitry in the acquisition and expression of episodic memories.

Action Potentials↗
PubMed2006

From grid cells to place cells: a mathematical model.

Anatomical connectivity and recent neurophysiological results imply that grid cells in the medial entorhinal cortex are the principal cortical inputs to place cells in the hippocampus. The authors propose a model in which place fields of hippocampal pyramidal cells are formed by linear summation of appropriately weighted inputs from entorhinal grid cells. Single confined place fields could be formed by summing input from a modest number (10-50) of grid cells with relatively similar grid phases, diverse grid orientations, and a biologically plausible range of grid spacings. When the spatial phase variation in the grid-cell input was higher, multiple, and irregularly spaced firing fields were formed. These observations point to a number of possible constraints in the organization of functional connections between grid cells and place cells.

Animals↗
PubMed2006

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

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

Animals↗
PubMed2005

Place cells, spatial maps and the population code for memory.

The study of population dynamics in hippocampal place cells has emerged as one of the most powerful tools for understanding the encoding, storage and retrieval of declarative memory. Recent work has laid out the contours of an attractor-based hippocampal population code for memory in recurrent circuits of the hippocampus. The code is based on inputs from a topographically organized, path-integration-dependent spatial map that lies upstream in the medial entorhinal cortex. The recurrent networks of the hippocampal formation enable these spatial inputs to be synthesized with nonspatial event-related information.

Animals↗
PubMed2005

Progressive transformation of hippocampal neuronal representations in "morphed" environments.

Hippocampal neural codes for different, familiar environments are thought to reflect distinct attractor states, possibly implemented in the recurrent CA3 network. A defining property of an attractor network is its ability to undergo sharp and coherent transitions between pre-established (learned) representations when the inputs to the network are changed. To determine whether hippocampal neuronal ensembles exhibit such discontinuities, we recorded in CA3 and CA1 when a familiar square recording enclosure was morphed in quantifiable steps into a familiar circular enclosure while leaving other inputs constant. We observed a gradual noncoherent progression from the initial to the final network state. In CA3, the transformation was accompanied by significant hysteresis, resulting in more similar end states than when only square and circle were presented. These observations suggest that hippocampal cell assemblies are capable of incremental plastic deformation, with incongruous information being incorporated into pre-existing representations.

Action Potentials↗
PubMed2005

Independent codes for spatial and episodic memory in hippocampal neuronal ensembles.

Hippocampal neurons were recorded under conditions in which the recording chamber was varied but its location remained unchanged versus conditions in which an identical chamber was encountered in different places. Two forms of neuronal pattern separation occurred. In the variable cue-constant place condition, the firing rates of active cells varied, often over more than an order of magnitude, whereas the location of firing remained constant. In the variable place-constant cue condition, both location and rates changed, so that population vectors for a given location in the chamber were statistically independent. These independent encoding schemes may enable simultaneous representation of spatial and episodic memory information.

Animals↗
PubMed2005

Microstructure of a spatial map in the entorhinal cortex.

The ability to find one's way depends on neural algorithms that integrate information about place, distance and direction, but the implementation of these operations in cortical microcircuits is poorly understood. Here we show that the dorsocaudal medial entorhinal cortex (dMEC) contains a directionally oriented, topographically organized neural map of the spatial environment. Its key unit is the 'grid cell', which is activated whenever the animal's position coincides with any vertex of a regular grid of equilateral triangles spanning the surface of the environment. Grids of neighbouring cells share a common orientation and spacing, but their vertex locations (their phases) differ. The spacing and size of individual fields increase from dorsal to ventral dMEC. The map is anchored to external landmarks, but persists in their absence, suggesting that grid cells may be part of a generalized, path-integration-based map of the spatial environment.

Action Potentials↗
PubMed2005

Spatial memory in the rat requires the dorsolateral band of the entorhinal cortex.

The extensive connections of the entorhinal cortex with the hippocampus and the neocortex point to this region as a major interface in the hippocampal-neocortical interactions underlying memory. We asked whether hippocampal-dependent recall of spatial memory depends on the entorhinal cortex, and, if so, which parts are critical. After training in a Morris water maze, rats received fiber-sparing lesions in the dorsolateral band of the entorhinal cortex, which mediates much of the visuospatial input to the dorsal hippocampus. These lesions entirely disrupted retention and retarded new learning. Spatial memory was spared by lesions in the ventromedial band, which connects primarily with ventral hippocampus, but these lesions reduced defensive behavior on an elevated plus maze, mirroring the effects of damage to ventral hippocampus. The results suggest that the functional differences between dorsal and ventral hippocampus reflect their connectivity with modules of the entorhinal cortex that are differently linked to the rest of the cortex.

Animals↗
PubMed2005

Spatial learning with unilateral and bilateral hippocampal networks.

This study investigated the ability of animals to learn both reference memory and delayed matching-to-place variants of the watermaze after large lesions of the hippocampus that deliberately spared only small remnants of the structure. Groups were created that had differing blocks of residual tissue in the septal pole of the hippocampus (15% or 30% of total volume), located either unilaterally (30 or 50% on one side, 0% on the other) or bilaterally (30 + 30%). These groups were capable of learning the reference memory task, as indexed by normal spatially focused searching in a probe trial, but their rate of learning was slower than that of sham-lesioned rats. An impairment in the rate of learning was also seen in the delayed match-to-place task, where one-trial memory was observed only at the shortest (5 s) intertrial interval in the lesioned groups with the largest sparing. In both tasks performance was proportional to the volume of hippocampus spared and independent of whether this was unilaterally or bilaterally located. The findings are compatible with distributed processing accounts of hippocampal memory storage.

Analysis of Variance↗
PubMed2004

Ensemble dynamics of hippocampal regions CA3 and CA1.

Computational models based on hippocampal connectivity have proposed that CA3 is uniquely positioned as an autoassociative memory network, capable of performing the competing functions of pattern completion and pattern separation. Recently, three independent studies, two using parallel neurophysiological recording methods and one using immediate-early gene imaging, have examined the responses of CA3 and CA1 ensembles to alterations of environmental context in rats. The results provide converging evidence that CA3 is capable of performing nonlinear transformations of sensory input patterns, whereas CA1 may represent changes in input in a more linear fashion.

Animals↗
PubMed2004

Spatial representation in the entorhinal cortex.

As the interface between hippocampus and neocortex, the entorhinal cortex is likely to play a pivotal role in memory. To determine how information is represented in this area, we measured spatial modulation of neural activity in layers of medial entorhinal cortex projecting to the hippocampus. Close to the postrhinal-entorhinal border, entorhinal neurons had stable and discrete multipeaked place fields, predicting the rat's location as accurately as place cells in the hippocampus. Precise positional modulation was not observed more ventromedially in the entorhinal cortex or upstream in the postrhinal cortex, suggesting that sensory input is transformed into durable allocentric spatial representations internally in the dorsocaudal medial entorhinal cortex.

Action Potentials↗
PubMed2004

Distinct ensemble codes in hippocampal areas CA3 and CA1.

The hippocampus has differentiated into an extensively connected recurrent stage (CA3) followed by a feed-forward stage (CA1). We examined the function of this structural differentiation by determining how cell ensembles in rat CA3 and CA1 generate representations of rooms with common spatial elements. In CA3, distinct subsets of pyramidal cells were activated in each room, regardless of the similarity of the testing enclosure. In CA1, the activated populations overlapped, and the overlap increased in similar enclosures. After exposure to a novel room, ensemble activity developed slower in CA3 than CA1, suggesting that the representations emerged independently.

Action Potentials↗
PubMed2004

Hippocampal place cells demand attention.

Hippocampal representations of the environment are thought to play a fundamental role in the encoding, storage, and retrieval of declarative memory. In this issue of Neuron, Kentros and coworkers show that new hippocampal representations stabilize only when animals are attentive.

Animals↗
PubMed2003

Selective hippocampal lesions do not increase adrenocortical activity.

It has been proposed that the hippocampus exerts a tonic inhibitory influence on the hypothalamic-pituitary-adrenal (HPA) stress axis. This claim rests, in particular, on the upregulation of corticosterone secretion and other measures of HPA activity after nonselective lesions of the hippocampal formation. We measured plasma corticosterone concentrations after selective neurotoxic damage to the hippocampus and the subiculum in rats. Concentrations were estimated during rest in the rat's home cage and at several time points after varying degrees of stress. Lesions of the hippocampus did not increase the concentration of corticosterone relative to control rats in any condition. Temporary inactivation of the hippocampus or the ventral subiculum by infusion of the GABAA receptor agonist muscimol also failed to induce hypersecretion, although hippocampal infusions did impair spatial memory. These results suggest that the hippocampus is not necessary for tonic inhibition of adrenocortical activity and imply that the HPA axis receives efficient negative feedback inhibition from other brain systems too.

Adrenal Cortex↗
PubMed2003

One-shot memory in hippocampal CA3 networks.

The hippocampus plays a crucial role in the encoding and retrieval of episodic memory. In this issue of Neuron, Nakazawa and coworkers show that synaptic modification in hippocampal CA3 neurons is critical for immediate storage of information, a key feature of episodic memory.

Animals↗