Grid cells

My talk will consist of three subtopics. The brain remembers episodes not in isolation but with their contextual relationships, such as spatial or temporal proximity. This is an essential feature of the brain’s memory, but the underlying mechanism is yet to be explored. Cell assemblies, or engrams, may provide neural representations for such relationships. First, I will show a class of associative memory models that encode and retrieve multiple memory contents linked by an arbitrary graph structure through experience and demonstrate the crucial role of the balance between two inhibitory subnet

Grid cells in the medial entorhinal cortex (MEC) of mammalian brains show hexagonal firing fields and are thought to encode the animal’s current location in the environment. As the animal moves, grid cells integrate self-motion cues to track the current position relative to a starting reference location. Recent experiments have identified a class of predictive grid cells that encode the animal’s upcoming location 1,2. Continuous attractor networks (CAN) explain how grid cells develop their characteristic hexagonal firing pattern and enable path integration. But how does predictive coding arise

Reconciling theoretical models with experimental data is a major challenge in neuroscience. We investigate how neurons that exhibit disorderly properties individually can produce orderly collective dynamics. Focusing on continuous-attractor networks, which model representations of continuous variables such as head direction and spatial location, we address the discrepancy between the symmetry required by these models and its apparent absence in mammalian neural recordings. Analysis of mouse head-direction cell tuning curves reveals significant heterogeneity that violates basic assumptions of c

…space, suggested by spatially tuned cells (place cells, grid cells, etc.) recorded in nonhuman animals. In an attempt to reconcile the two views, we use a memory-augmented neural network in a reinforcement learning setup to solve a navigation task in a simulated maze. The key feature of the model is that it learns autonomously what and when to store into, and retrieve from, an external memory buffer. Once the mode

Grid cells are neurons in the entorhinal cortex that are thought to perform computations in support of spatial navigation. As direct recordings of grid cells from the human brain are only rarely possible, functional magnetic resonance imaging (fMRI) studies proposed and described an indirect measure of entorhinal grid-cell activity, which is quantified as a hexadirectional modulation (HM) of fMRI activity as a function of the subject’s movement direction through a virtual environment. However, the contributing role of the aggregated activity of grid cells to this modulation remains unclear. Ou

Grid cells are believed to be key neurons in spatial navigation. Their mechanisms and operation have been described via the theoretical framework of continuous attractor networks (CANs). While increasing evidence points to a CAN mechanism for grid cells, one fundamental aspect of grid cell CAN models remains untested, namely the prediction that population activity is determined by specific patterns of recurrent connectivity. In particular, many CAN models require a Mexican hat connectivity profile with excitatory connections between functionally similar neurons and inhibition between more diss

Grid cells, which were first discovered in the entorhinal cortex of mammals, are normatively thought of as instrumental in spatial navigation because of their periodic firing characteristics as the animal traverses its surroundings. In recent years, converging bodies of evidence from etiological and teleological investigations of grid cells indicate that they arise under efficient coding schemes, with metabolic, sparsity, and nonnegativity constraints supporting the formation of regular lattices that approximate what has been observed in animal experiments. Here we import the notion of local a

…In this study, we found fewer grid cells with reduced spatial stability in old mice. We compared gene expression profiles between young and old mice using 10x Genomics Visium technology. Among 1664 differentially expressed genes, we discovered a marker gene for subpopulation in MEC Layer III with decreased cell number with age. Silen

The entorhinal cortex is a crucial hub for the coding of animals’ experiences in space. Grid cells, key components of this network, exhibit multiple firing fields that tessellate the environment as a function of the animals’ location. At the population level, the dynamics of the grid cell network reside on a toroidal manifold, irrespective of the sensory inputs or behavioral state, in agreement with continuous attractor networks (CAN) theories.However, the developmental origin of toroidal topology remains to be determined. Using Neuropixels 2.0 we obtained high-density population recordings in

Antibiotics are tremendously beneficial in reducing mortality rates by combating infections but their excessive use has led to severe antibiotic resistance worldwide. The ingestion of oral antibiotics dramatically alters the gut microbiome. Critically, there is limited understanding of the effects of a dysfunctional microbiome on brain function. Male C57BL/6J mice (2–4 months) were given drinking water containing antibiotics (ABX group; ampicillin, neomycin, gentamicin, metronidazole, and vancomycin) or untreated water (CON group). Separate cohorts received butyrate, a key microbiome-derived m

The entorhinal cortex is an area known to be involved in spatial navigation and episodic memories. While the spatial aspects of episodic memories have been studied in great detail, questions still remain regarding the processing of social information in the brain.Emerging evidence points towards a complex network of brain areas involved in social memory processing. In particular, the hippocampal regions CA2 and ventral CA1 play an important role, but the role of computations within the hippocampus compared to the input regions remains unresolved. With entorhinal cortex being the main input reg

…shown that single hippocampal place cells represent different locations in different spaces – a functio

The grid cells in the entorhinal cortex play fundamental roles in spatial navigation. However, it has been unclear whether they contribute to predicting an animal’s future location or determining its future trajectory. In this study, we performed large-scale extracellular recordings from the medial entorhinal cortex together with hippocampal CA1 of rats moving toward a destination in the square arena. We found a subset of grid cells in the medial entorhinal cortex that represent grid fields when rate maps are estimated based on future animal locations, but these cells did not show grid field b

Grid cells of the medial entorhinal cortex (MEC) have been proposed to play a key role in navigation. Competing models suggest they contribute to spatial localisation in general or have a dedicated role in path integration. Here, we aim to distinguish these possibilities by investigating how grid and non-grid cell firing varies as a function of performance in a virtual reality location memory task that can be solved either with a cued-based strategy or exclusively by path integration. We take advantage of spontaneous variation within and between recording sessions, which gives a complementary

…specialized cell types such as place cells, grid cells, and head direction cells. Avian species like titmice, quails, barn owls, streaked shearwaters, and black-capped chickadees also exhibit these cell types. Despite pigeons demonstrating remarkable spatial cognition and navigation abilities, the neural basis remains poorly understood. Previous research suggests that spatial coding in neurons, such as place cells, can be influenced by factors like distances from walls or env

Quantifying the contribution of dynamically changing neural activity to goal-directed behaviors is a longstanding problem in neuroscience. One approach is to systematically test how behaviors map to individual firing rates at each time step, but it is less clear how behaviors map to complex neural latent dynamics. In recent years deep learning approaches have become powerful tools to extract these latent dynamics (Schneider, Lee, Mathis 2023), yet how to probe them in order to attribute input neurons to latents remains challenging. Gradient-based attribution is one of the methods that aim to e

Pathological amyloid beta (Aβ) accumulation in the brain has been associated with poor cognitive performance and aberrant neuronal activity in preclinical mouse models of Alzheimer’s disease (AD). Here, we assessed the impact of advanced Aβ pathology on spatial information processing in the medial entorhinal cortex (MEC) of 18-month APP NL-G-F knock-in mice as they explored contextually novel and familiar open field arenas in a two-day, four-session recording paradigm. Using in vivo electrophysiology, we tracked single-units across all sessions and found that MEC single-unit spatial informatio

…we recently discovered that fan cells in the LEC send direct projections to MEC, suggesting that spatial and object information could be integrated within MEC (Vandrey et al. 2022, doi:10.7554/eLife.83008). Evidence for object-related firing in the MEC is consistent with this possibility, but whether LEC projections influence spatial and obje

The aim of this project is to characterize how grid cells code spatial information during goal-directed navigation. Previous studies on the effect of goal on grid cells activity merged goal location with reward, making difficult to conclude about the nature of the information (i.e. location or reward) integrated by the grid cells network. We used a continuous-goal directed navigation task which allows separating spatial goal from the reward. We found a local distortion of the grid map around the goal that only emerges when a halt inside the goal zone is required to obtain the reward. This indi

…functions of the EC such as grid cells, border cells, speed cells or head-direction cells. These cell types have been characterized based on their firing properties, however, still lack a molecular profile. Similarly, detailed anatomical cell types have been described within the different EC layers, including ste

…in the parahippocampal areas, such as grid cells and place cells, show pronounced theta modulation. Grid cells in the medial entorhinal cortex (MEC) are theta modulated during active wakefulness, with power and frequency correlating to e.g. running speed or environmental familiarity. Suppressin

…is achieved through canonical feature cells like grid, object vector, head direction and border cells that are located in the superficial layers of MEC but their exact anatomical organization remains to be determined. Previous work has shown that the grid cell network consists of discrete modules of increasing scale along the dorsal-ventral axis of MEC. In addition, recent imaging studies have hinted at a clustering of grid cells towards the medial part of MEC. However, due to technical limitations f

…which has been suggested to rely on grid cells that the EC is known to harbor. On population level, grid cells exhibit a six-fold rotational symmetry as a function of gaze direction, wh

…of this internal map, as it contains grid cells that fire periodically in space. However, grid cells are also active at rest, replaying grid cell spike sequences that reflect spatial sequences observed during mobility [1,2,3]. Replay events are thought to play an important role in memory and planning. Little is known, however, on the spatial structure of entorhinal replay, limiting our understanding of how grid cells partici