Biology subjects

Nagelhus, A.

Publications and source records attributed to Nagelhus, A..

3 recordsLinked to original sources

bioRxiv2025

Functional independence of entorhinal grid cell modules enables remapping in hippocampal place cells

A systems-level understanding of cortical computation requires insight into how neural codes are transformed across distinct brain circuits. In the mammalian cortex, one of the few systems where such transformations are tractable is the spatial mapping circuit. This circuit comprises interconnected regions of medial entorhinal cortex (MEC) and hippocampus, which encode location using fundamentally different neural codes. A key distinction is that neural activity in MEC, including that of directionally tuned cells and grid cells, evolves along low-dimensional manifolds, preserving stable phase relationships across different environments and behaviors1-8. In contrast, hippocampal place cells frequently undergo global remapping: their collective firing patterns reorganize randomly across different environments9-12, revealing an apparently limitless repertoire of orthogonal spatial representations12-14. The mechanisms by which spatial maps are transformed between the two coding schemes remain unresolved. Here, we used large-scale multi-area Neuropixels recordings to show that when rats were transferred from one familiar environment to another, each module of grid cells underwent a unique change in phase on its low-dimensional manifold, at the same time as simultaneously recorded place cells exhibited global remapping. In contrast, training conditions that produced smaller differences in the phase shifts of simultaneously recorded grid modules resulted in incomplete place cell remapping, mirroring previous reports of partial remapping15-19. Hippocampal remapping was not associated with rotational differences between grid modules under any condition. Taken together, these findings suggest that differential phase shifts across grid cell modules form the basis for the orthogonalization of downstream hippocampal spatial codes during remapping. The transformation from low-dimensional spatial representations in the MEC to high-dimensional codes in the hippocampus may underlie the hippocampus ability to support high-capacity memory storage3,13,14,20-22.

neuroscience↗

bioRxiv2022

Object-centered population coding in CA1 of the hippocampus

Objects and landmarks are crucial for guiding navigation and must be integrated into the cognitive map of space. Studies of object coding in the hippocampus have primarily focused on activity of single cells. Here we record simultaneously from large numbers of hippocampal CA1 neurons to determine how the presence of a salient object in the environment alters single-neuron and neural-population dynamics of the area. Only a small number of cells fired consistently at the object location, or at a fixed distance and direction from it; yet the majority of the cells showed some change in their spatial firing patterns when the object was introduced. At the neural population level, these changes were systematically organized according to the animals distance from the object. This organization was widely distributed across the cell sample, suggesting that some features of cognitive maps - including object representation - are best understood as emergent properties of neural populations.

neuroscience↗

bioRxiv2021

Grid-cell modules remain coordinated when neural activity is dissociated from external sensory cues

The representation of an animals position in the medial entorhinal cortex (MEC) is distributed across several modules of grid cells, each characterized by a distinct spatial scale. The population activity within each module is tightly coordinated and preserved across environments and behavioral states. Little is known, however, about the coordination of activity patterns across modules. We analyzed the joint activity patterns of hundreds of grid cells simultaneously recorded in animals that were foraging either in the light, when sensory cues could stabilize the representation, or in darkness, when such stabilization was disrupted. We found that the states of different grid modules are tightly coordinated, even in darkness, when the internal representation of position within the MEC deviates substantially from the true position of the animal. These findings suggest that internal brain mechanisms dynamically coordinate the representation of position in different modules, to ensure that grid cells jointly encode a coherent and smooth trajectory of the animal.

neuroscience↗