Biology subjects

Lykken, C. M.

Publications and source records attributed to Lykken, C. M..

4 recordsLinked to original sources

bioRxiv2026

Toroidal topology of grid-cell activity precedes spatial navigation during development

The medial entorhinal cortex (MEC) is a central component of the mammalian navigation system1-5, in which spatially and directionally tuned neurons, including grid cells and head-direction cells, encode an animals position and orientation6-8. These cells form internal maps with periodic topologies: head-direction cells traverse ring-like manifolds9,10, while grid cells are organized on toroidal manifolds11. The persistence of these topologies across behavioral states and environments11,12 raises the possibility that they arise intrinsically from network architecture rather than through sensory experience4,5,13-17. Consistent with this view, observations in juvenile rats have shown that rudimentary spatial tuning appears in place cells, head direction cells and grid cells almost as soon as pups begin to explore their surroundings at 2-3 weeks of age18-20. However, it remains unclear whether spatial experience is required for the initial emergence of positional tuning and for the organization of tuned cells into periodic maps. Here we show, using large-scale ensemble recordings in rat pups, that toroidal manifolds emerge in MEC subnetworks as early as postnatal day 10 (P10), preceding eye and ear opening, upright posture, quadrupedal gait, and active exploration21,22. These toroidal networks were modular from the beginning, with increasing differentiation of their dynamics appearing on P11-12. The onset of toroidal topology coincided with a transition in MEC network activity characterized by desynchronization and increased inhibitory connectivity, a developmental shift observed broadly across cortical regions at this age23,24. In contrast, ring-like manifolds were already detectable by P9, with traces of directional tuning appearing in individual cells at P8 -- consistent with an earlier maturation of subcortical circuitry25. As pups subsequently began to explore the environment around P15-16, these internally generated maps progressively aligned with external landmarks, culminating in stable, periodic firing fields by three weeks of age. Taken together, these findings identify ring-like and toroidal manifolds as instinctive computational motifs of the developing brain. Their early emergence, preceding major sensory input and navigation, supports the view that spatial representations are preconfigured and later anchored to the external world through experience-dependent plasticity.

neuroscience↗

bioRxiv2026

Reproducible and predictable reorganization of place fields driven by grid subfield rate changes

Understanding how the brain constructs stable yet flexible maps of space remains a central challenge in neuroscience. Place cells in the hippocampus fire at specific locations in a given environment, but reorganize completely upon introduction to another environment in a process called remapping. The medial entorhinal cortex (MEC) provides a major cortical input to the hippocampus, and the spatially periodic firing patterns of its grid cells are thought to contribute to place field formation. We previously showed that chemogenetic depolarization of MEC layer II stellate cells selectively altered firing rates within individual grid cell subfields, impaired spatial memory, and induced a form of reversible place cell remapping that we called artificial remapping. However, it remains unclear whether artificial remapping reflects a reproducible and stable mapping from entorhinal inputs to place cell outputs or a random reorganization of place fields. To explore the transfer of information between MEC and hippocampus, we repeated this chemogenetic manipulation on consecutive days and found that stimulating the same stellate cells produced similar changes in both grid subfield rates and place field locations. Using both experimental and simulated data, we show that baseline place cell activity patterns could be used to predict place field locations following the manipulation. These findings provide direct evidence for consistent input-output relationships in the entorhinal-hippocampal system and point to a central role for grid subfield rate changes in the reorganization of hippocampal spatial representations.

neuroscience↗

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↗

bioRxiv2024

Event structure sculpts neural population dynamics in the lateral entorhinal cortex

Our experience of the world is a continuous stream of events which must be segmented and organized simultaneously at multiple timescales. The neural mechanisms underlying this process remain unknown. Here, we simultaneously recorded many hundreds of neurons in the lateral entorhinal cortex (LEC) of freely behaving rats as we manipulated event structure at multiple timescales. During foraging as well as during sleep, population activity drifted continuously and unidirectionally along a one-dimensional manifold. Boundaries between events were associated with discrete shifts in state space, suggesting that LEC dynamics directly reflect event segmentation. During tasks with a recurring temporal structure, activity traveled additionally in directions orthogonal to the flow of drift, enabling the LEC population to multiplex event information across different timescales. Taken together, these results identify a hierarchically organized neural coding scheme for segmenting and organizing events in time.

neuroscience↗