Entorhinal cortex

The human medial temporal lobe contains neurons that respond selectively to the semantic contents of a presented stimulus. These "concept cells" may respond to very different pictures of a given person and even to their written or spoken name. Their response latency is far longer than necessary for object recognition, they follow subjective, conscious perception, and they are found in brain regions that are crucial for declarative memory formation. It has thus been hypothesized that they may represent the semantic "building blocks" of episodic memories. In this talk I will present data from

How can the hippocampal system transition from episodic one-shot learning to a multi-shot learning regime and what is the utility of the resultant neural representations? This talk will explore the role of the dentate gyrus (DG) anatomy in this context. The canonical DG model suggests it performs pattern separation. More recent experimental results challenge this standard model, suggesting DG function is more complex and also supports the precise binding of objects and events to space and the integration of information across episodes. Very recent studies attribute pattern separation and patte

The entorhinal cortex (EC) sits at a critical junction where sensory input and higher-level processing converge and is necessary for learning interval timing and relating durations in distinct temporal contexts[1]. “Time cells” in the medial subdivision of the EC (MEC) tile task durations during a temporal variant of the Delay Non-match to Sample (tDNMS) task in which animals must detect non-matching durations. Over training, subpopulations of MEC time cells become context-dependent showing differential activity across different trial types. While attractor models of EC activity predict experi

…which receive inputs from the CA3 and entorhinal cortex (EC). No widely accepted network-based theory for place field formation exists, but many models offer mechanisms for place-field firing. One type of hypotheses proposes that it results from summated output of spatially tuned cells, like grid cells or boundary vector cells. Another suggests CA1 place fields are replicate of CA3 place fie

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

…regions (such as hippocampus and entorhinal cortex) have recurrent architectures, it is unclear if this feedforward association mechanism is the only way in which spatial memories can be stored. Here, we propose a new mechanism for spatial memory that is derived from reverse-engineering recurrent neural networks (RNNs). We train RNNs on a spatial navigation task posed as a rein

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

…to long-term memories in the cortex. How this process exactly takes place at the neuronal level, however, is still largely unknown. To answer this question, we leveraged a large publicly available dataset of simultaneous Neuropixels recordings across the brain from the International Brain Laboratory collaboration. We analyzed 74

Despite extensive research into the classic subfields of the hippocampus, the fasciola cinerea (FC), a medially located structure within the hippocampal formation, remains understudied. In order to gain insight into the unique features and potential functions of the FC, we examined the morphology, physiology, and connectivity of its principal neurons in anesthetized mice. Using in-vivo single-cell juxtacellular recording-labeling and quantitative morphometric analysis, we found that FC neurons exhibit unique firing patterns and dendritic architectures, which are distinct from principal cell po

Unlike familiar Alzheimer’s Disease (FAD) which is caused by mutations, most common sporadic disease (SAD) arises from a combination of risk factors including inflammation. This study aimed to explore and compare the effects of two pro-inflammatory agents: Western-diet (WD) and Lipopolysaccharide (LPS) of Gram-negative bacteria on initiation of AD molecular markers in the brain in the absence of AD mutations. To this aim, 3 months-old (mo) male C57BL/6J mice were divided into 3 groups: fed with WD, with Standard Diet (SD-CTR) and SD-fed mice injected 3 times with LPS (0.5mg/kg) at 3 mo. Mice w

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

…(NFTs) have been identified in the entorhinal cortex and olfactory bulbs, both crucial in olfactory information processing. We therefore investigated the hypothesis that typical ND lesions could appear early in olfactory system regions.We used a tauopathy mouse model (PS19 mice) expressing the human tau protein (1N4R) carrying the P301S mutation. PS19 mice develop NFTs-like inclusions at six months, leading to progr

…N-ACA was demonstrated in the entorhinal cortex region after the 4-AP-induced seizure model. Furthermore, to shed light on the

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

The entorhinal cortex (EC) connects to the hippocampus sending different information from cortical areas that is first processed at the dentate gyrus (DG) including spatial, limbic, and sensory and information. Excitatory afferents from lateral (LPP) and medial (MPP) perforant pathways of the EC connecting to granule cells (GC) of the DG play a role in memory encoding and information processing. LPP- and MPP-GC synapses have distinct electrophysiological properties, and these differences potentially affecting the functional processing of information. However, the plasticity of these synapses i

The deep layers (V/VI) of the entorhinal cortex constitute a major relay station for routing neuronal activity from the hippocampus to downstream networks. To identify contributing pathways, we recently investigated the structural and functional organization of hippocampal projections to layer V (LV) of the medial entorhinal cortex (MEC) (Ohara, Rannap et al., Cell Rep. 2023). Here, we performed whole-cell patch-clamp recordings from MEC-LVI neurons combined with field potential recordings from hippocampal area CA1 in horizontal mouse brain slices. We found that a spontaneously occurring hippo

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

Structural motif analysis seeks to better understand brain connectivity by interrogating the long-range axonal projections that link distant brain regions at the single-cell resolution. This approach is enabled by MAPseq, a novel experimental methodology which labels cellular projections with viral barcodes. This recontextualizes single-neuron tracing as a problem of sequencing, overcoming the throughput limitations of prior optical techniques and capitalizing on the swift advancement of modern sequencing technology.Current MAPseq-based long range projection motif analysis methods rely on the

…most superficial layer of the cerebral cortex, providing a transient source of excitatory inputs to immature pyramidal neurons. In the murine brain, CR cells are greatly reduced in the neocortex after postnatal week two, whereas in hippocampus, they persist throughout postnatal development and even into adulthood. During this time, they are integrated in the CA1 network, and recent work (Glærum et al. 2024) has showed that their persiste

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

…and, at later stages, in prefrontal cortex (PFC) which ultimately self-governs storage and retrieval of remote memory. Whether and how systems consolidation develops in mouse models of Alzheimer’s disease (AD) is unknown. We previously reported that 2-month-old pre-symptomatic Tg2576 AD mice trained for contextual fear conditioning (CFC) exhibit intact recent memory without activating the HIP but, instead, over-activating the BLA. Here

…relies on the hippocampus (HP) and the entorhinal cortex (EC). The superficial layers of the EC provide the primary input to the HP via the perforant path, so we use a mouse line capable of expressing chemogenetic inhibitors in a particular set of projection neurons of EC Layer II (EC stellate and fan cells) to examine the precise role played by EC inputs in different forms of episodic memory. For this we employ an episodic memory task with both olfactory and spatial twin variants. Both are iden

The entorhinal cortex (EC) plays a pivotal role in memory functions and spatial navigation, connecting the hippocampus with the neocortex. This brain region integrates a wide range of cortical and subcortical inputs and it is one of the first brain regions affected by Alzheimer´s disease. However, its synaptic organization in the human brain is largely unknown due to the difficulties involved in studying the human brain via electron microscope techniques. Here, we used Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) to perform a 3D analysis of the synapses in all layers of the medial E

One of the most fascinating properties of the brain is its ability to adjust behaviors, which typically results from experience-dependent modifications of neuronal circuits. Synaptic plasticity refers to changes in synaptic strength at pre-existing synapses induced by transient activity. By modifying neural circuit flow, synaptic plasticity is believed to play a central role in the capacity of the brain to incorporate new experiences into persistent memories. Long-term potentiation has emerged as a prominent mechanism associated with learning and memory. Protein synthesis is well-recognized as