Functional subregions of the human entorhinal cortex.
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ABSTRACT:
SUBMITTER: Maass A
PROVIDER: S-EPMC4458841 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The ability to remember and navigate spatial environments is critical for everyday life. A primary mechanism by which the brain represents space is through hippocampal place cells, which indicate when an animal is at a particular location. An important issue is understanding how the hippocampal place-cell network represents specific properties of the environment, such as signifying that a particular position is near a doorway or that another position is near the end of a corridor. The entorhinal cortex (EC), as the main input to the hippocampus, may play a key role in coding these properties because it contains neurons that activate at multiple related positions per environment. We examined the diversity of spatial coding across the human medial temporal lobe by recording neuronal activity during virtual navigation of an environment containing four similar paths. Neurosurgical patients performed this task as we recorded from implanted microelectrodes, allowing us to compare the human neuronal representation of space with that of animals. EC neurons activated in a repeating manner across the environment, with individual cells spiking at the same relative location across multiple paths. This finding indicates that EC cells represent non-specific information about location relative to an environment's geometry, unlike hippocampal place cells, which activate at particular random locations. Given that spatial navigation is considered to be a model of how the brain supports non-spatial episodic memory, these findings suggest that EC neuronal activity is used by the hippocampus to represent the properties of different memory episodes.
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Project description:Finding our way in spatial environments is an essential part of daily life. How do we come to possess this sense of direction? Extensive research points to the hippocampus and entorhinal cortex (EC) as key neural structures underlying spatial navigation. To better understand this system, we examined recordings of single-neuron activity from neurosurgical patients playing a virtual-navigation video game. In addition to place cells, which encode the current virtual location, we describe a unique cell type, EC path cells, the activity of which indicates whether the patient is taking a clockwise or counterclockwise path around the virtual square road. We find that many EC path cells exhibit this directional activity throughout the environment, in contrast to hippocampal neurons, which primarily encode information about specific locations. More broadly, these findings support the hypothesis that EC encodes general properties of the current context (e.g., location or direction) that are used by hippocampus to build unique representations reflecting combinations of these properties.
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Project description:Remembering event sequences is central to episodic memory and presumably supported by the hippocampal-entorhinal region. We previously demonstrated that the hippocampus maps spatial and temporal distances between events encountered along a route through a virtual city (Deuker et al., 2016), but the content of entorhinal mnemonic representations remains unclear. Here, we demonstrate that multi-voxel representations in the anterior-lateral entorhinal cortex (alEC) - the human homologue of the rodent lateral entorhinal cortex - specifically reflect the temporal event structure after learning. Holistic representations of the sequence structure related to memory recall and the timeline of events could be reconstructed from entorhinal multi-voxel patterns. Our findings demonstrate representations of temporal structure in the alEC; dovetailing with temporal information carried by population signals in the lateral entorhinal cortex of navigating rodents and alEC activations during temporal memory retrieval. Our results provide novel evidence for the role of the alEC in representing time for episodic memory.
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Project description:The medial (MEC) and lateral entorhinal cortex (LEC), widely studied in rodents, are well defined and characterized. In humans, however, the exact locations of their homologues remain uncertain. Previous functional magnetic resonance imaging (fMRI) studies have subdivided the human EC into posteromedial (pmEC) and anterolateral (alEC) parts, but uncertainty remains about the choice of imaging modality and seed regions, in particular in light of a substantial revision of the classical model of EC connectivity based on novel insights from rodent anatomy. Here, we used structural, not functional imaging, namely diffusion tensor imaging (DTI) and probabilistic tractography to segment the human EC based on differential connectivity to other brain regions known to project selectively to MEC or LEC. We defined MEC as more strongly connected with presubiculum and retrosplenial cortex (RSC), and LEC as more strongly connected with distal CA1 and proximal subiculum (dCA1pSub) and lateral orbitofrontal cortex (OFC). Although our DTI segmentation had a larger medial-lateral component than in the previous fMRI studies, our results show that the human MEC and LEC homologues have a border oriented both towards the posterior-anterior and medial-lateral axes, supporting the differentiation between pmEC and alEC.
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Project description:Knowing where we are, where we have been, and where we are going is critical to many behaviors, including navigation and memory. One potential neuronal mechanism underlying this ability is phase precession, in which spatially tuned neurons represent sequences of positions by activating at progressively earlier phases of local network theta oscillations. Based on studies in rodents, researchers have hypothesized that phase precession may be a general neural pattern for representing sequential events for learning and memory. By recording human single-neuron activity during spatial navigation, we show that spatially tuned neurons in the human hippocampus and entorhinal cortex exhibit phase precession. Furthermore, beyond the neural representation of locations, we show evidence for phase precession related to specific goal states. Our findings thus extend theta phase precession to humans and suggest that this phenomenon has a broad functional role for the neural representation of both spatial and non-spatial information.
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Project description:Layer II of the medial entorhinal cortex (MEC) contains two principal cell types: pyramidal cells and stellate cells. Accumulating evidence suggests that these two cell types have distinct molecular profiles, physiological properties, and connectivity. The observations hint at a fundamental functional difference between the two cell populations but conclusions have been mixed. Here, we used a tTA-based transgenic mouse line to drive expression of ArchT, an optogenetic silencer, specifically in stellate cells. We were able to optogenetically identify stellate cells and characterize their firing properties in freely moving mice. The stellate cell population included cells from a range of functional cell classes. Roughly one in four of the tagged cells were grid cells, suggesting that stellate cells contribute not only to path-integration-based representation of self-location but also have other functions. The data support observations suggesting that grid cells are not the sole determinant of place cell firing.
| S-EPMC6140717 | biostudies-literature
Project description:The entorhinal cortex (EC) is a brain region that has been shown to be essential for memory functions and spatial navigation. However, detailed three-dimensional (3D) synaptic morphology analysis and identification of postsynaptic targets at the ultrastructural level have not been performed before in the human EC. In the present study, we used Focused Ion Beam/Scanning Electron Microscopy to perform a 3D analysis of the synapses in the neuropil of medial EC in layers II and III from human brain autopsies. Specifically, we studied synaptic structural parameters of 3561 synapses, which were fully reconstructed in 3D. We analyzed the synaptic density, 3D spatial distribution, and type (excitatory and inhibitory), as well as the shape and size of each synaptic junction. Moreover, the postsynaptic targets of synapses could be clearly determined. The present work constitutes a detailed description of the synaptic organization of the human EC, which is a necessary step to better understand the functional organization of this region in both health and disease.
| S-EPMC7727377 | biostudies-literature
Project description:The grid-like activity pattern of cells in the mammalian entorhinal cortex provides an internal reference frame for allocentric self-localization. The same neurons maintain robust phase couplings with local field oscillations. We found that neurons of the human entorhinal cortex display consistent spatial and temporal phase locking between spikes and slow gamma band local field potentials (LFPs) during virtual navigation. The phase locking maintained an environment-specific map over time. The phase tuning of spikes to the slow gamma band LFP revealed spatially periodic phase grids with environment-dependent scaling and consistent alignment with the environment. Using a Bayesian decoding model, we could predict the avatar's position with near perfect accuracy and, to a lesser extent, that of heading direction as well. These results imply that the phase of spikes relative to spatially modulated gamma oscillations encode allocentric spatial positions. We posit that a joint spatiotemporal phase code can implement the combined neural representation of space and time in the human entorhinal cortex.
| S-EPMC9067922 | biostudies-literature
Project description:IntroductionThe size and shape of neurons are important features indicating aging and the pathology of neurodegenerative diseases. Despite the significant advances of optical microscopy, quantitative analysis of the neuronal features in the human brain remains largely incomplete. Traditional histology on thin slices bears tremendous distortions in three-dimensional reconstruction, the magnitude of which are often greater than the structure of interest. Recently development of tissue clearing techniques enable the whole brain to be analyzed in small animals; however, the application in the human remains challenging.MethodsIn this study, we present a label-free quantitative optical coherence microscopy (OCM) technique to obtain the morphological parameters of neurons in human entorhinal cortex (EC). OCM uses the intrinsic back-scattering property of tissue to identify individual neurons in 3D. The area, length, width, and orientation of individual neurons are quantified and compared between layer II and III in EC.ResultsThe high-resolution mapping of neuron size, shape, and orientation shows significant differences between layer II and III neurons in EC. The results are validated by standard Nissl staining of the same samples.DiscussionThe quantitative OCM technique in our study offers a new solution to analyze variety of neurons and their organizations in the human brain, which opens new insights in advancing our understanding of neurodegenerative diseases.
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Project description:When participants performed a visual search task, functional MRI responses in entorhinal cortex exhibited a sixfold periodic modulation by gaze-movement direction. The orientation of this modulation was determined by the shape and orientation of the bounded search space. These results indicate that human entorhinal cortex represents visual space using a boundary-anchored grid, analogous to that used by rodents to represent navigable space.
| S-EPMC5801057 | biostudies-literature