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Journal articles on the topic 'Mammalian medial entorhinal cortex'

Author: Grafiati

Published: 6 September 2023

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1

Medina, Loreta, Antonio Abellán, and Ester Desfilis. "Contribution of Genoarchitecture to Understanding Hippocampal Evolution and Development." Brain, Behavior and Evolution 90, no. 1 (2017): 25–40. http://dx.doi.org/10.1159/000477558.

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The hippocampal formation is a highly conserved structure of the medial pallium that works in association with the entorhinal cortex, playing a key role in memory formation and spatial navigation. Although it has been described in several vertebrates, the presence of comparable subdivisions across species remained unclear. This panorama has started to change in recent years thanks to the identification of some of the genes that regulate the development of the hippocampal formation in the mouse and help to delineate its subdivisions based on molecular features. Some of these genes have been used to try to identify subdivisions in chicken and lizards comparable to those of the mammalian hippocampal formation and the entorhinal cortex. Here, we review some of these data, which suggest the existence of fields comparable to the dentate gyrus, CA3, CA1, subiculum, as well as medial and lateral parts of the entorhinal cortex in all amniotes. We also analyze available data suggesting the existence of serial connections between these fields, speculate on the possible existence of auto-associative loops in CA3, and discuss general principles governing the formation of the connections.

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2

Zhang, Sheng-Jia, Jing Ye, Jonathan J. Couey, Menno Witter, Edvard I. Moser, and May-Britt Moser. "Functional connectivity of the entorhinal–hippocampal space circuit." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1635 (February 5, 2014): 20120516. http://dx.doi.org/10.1098/rstb.2012.0516.

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The mammalian space circuit is known to contain several functionally specialized cell types, such as place cells in the hippocampus and grid cells, head-direction cells and border cells in the medial entorhinal cortex (MEC). The interaction between the entorhinal and hippocampal spatial representations is poorly understood, however. We have developed an optogenetic strategy to identify functionally defined cell types in the MEC that project directly to the hippocampus. By expressing channelrhodopsin-2 (ChR2) selectively in the hippocampus-projecting subset of entorhinal projection neurons, we were able to use light-evoked discharge as an instrument to determine whether specific entorhinal cell groups—such as grid cells, border cells and head-direction cells—have direct hippocampal projections. Photoinduced firing was observed at fixed minimal latencies in all functional cell categories, with grid cells as the most abundant hippocampus-projecting spatial cell type. We discuss how photoexcitation experiments can be used to distinguish the subset of hippocampus-projecting entorhinal neurons from neurons that are activated indirectly through the network. The functional breadth of entorhinal input implied by this analysis opens up the potential for rich dynamic interactions between place cells in the hippocampus and different functional cell types in the entorhinal cortex (EC).

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3

Cuneo, J., L. Barboni, N. Blanco, M. del Castillo, and J. Quagliotti. "ARM-Cortex M3-Based Two-Wheel Robot for Assessing Grid Cell Model of Medial Entorhinal Cortex: Progress towards Building Robots with Biologically Inspired Navigation-Cognitive Maps." Journal of Robotics 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/8069654.

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This article presents the implementation and use of a two-wheel autonomous robot and its effectiveness as a tool for studying the recently discovered use of grid cells as part of mammalian’s brains space-mapping circuitry (specifically the medial entorhinal cortex). A proposed discrete-time algorithm that emulates the medial entorhinal cortex is programed into the robot. The robot freely explores a limited laboratory area in the manner of a rat or mouse and reports information to a PC, thus enabling research without the use of live individuals. Position coordinate neural maps are achieved as mathematically predicted although for a reduced number of implemented neurons (i.e., 200 neurons). However, this type of computational embedded system (robot’s microcontroller) is found to be insufficient for simulating huge numbers of neurons in real time (as in the medial entorhinal cortex). It is considered that the results of this work provide an insight into achieving an enhanced embedded systems design for emulating and understanding mathematical neural network models to be used as biologically inspired navigation system for robots.

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Ye, Jing, Menno P. Witter, May-Britt Moser, and Edvard I. Moser. "Entorhinal fast-spiking speed cells project to the hippocampus." Proceedings of the National Academy of Sciences 115, no. 7 (January 31, 2018): E1627—E1636. http://dx.doi.org/10.1073/pnas.1720855115.

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The mammalian positioning system contains a variety of functionally specialized cells in the medial entorhinal cortex (MEC) and the hippocampus. In order for cells in these systems to dynamically update representations in a way that reflects ongoing movement in the environment, they must be able to read out the current speed of the animal. Speed is encoded by speed-responsive cells in both MEC and hippocampus, but the relationship between the two populations has not been determined. We show here that many entorhinal speed cells are fast-spiking putative GABAergic neurons. Using retrograde viral labeling from the hippocampus, we find that a subset of these fast-spiking MEC speed cells project directly to hippocampal areas. This projection contains parvalbumin (PV) but not somatostatin (SOM)-immunopositive cells. The data point to PV-expressing GABAergic projection neurons in MEC as a source for widespread speed modulation and temporal synchronization in entorhinal–hippocampal circuits for place representation.

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Sun, Chen, Takashi Kitamura, Jun Yamamoto, Jared Martin, Michele Pignatelli, Lacey J. Kitch, Mark J. Schnitzer, and Susumu Tonegawa. "Distinct speed dependence of entorhinal island and ocean cells, including respective grid cells." Proceedings of the National Academy of Sciences 112, no. 30 (July 13, 2015): 9466–71. http://dx.doi.org/10.1073/pnas.1511668112.

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Entorhinal–hippocampal circuits in the mammalian brain are crucial for an animal’s spatial and episodic experience, but the neural basis for different spatial computations remain unknown. Medial entorhinal cortex layer II contains pyramidal island and stellate ocean cells. Here, we performed cell type-specific Ca2+ imaging in freely exploring mice using cellular markers and a miniature head-mounted fluorescence microscope. We found that both oceans and islands contain grid cells in similar proportions, but island cell activity, including activity in a proportion of grid cells, is significantly more speed modulated than ocean cell activity. We speculate that this differential property reflects island cells’ and ocean cells’ contribution to different downstream functions: island cells may contribute more to spatial path integration, whereas ocean cells may facilitate contextual representation in downstream circuits.

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6

Krupic, Julija, Marius Bauza, Stephen Burton, Colin Lever, and John O'Keefe. "How environment geometry affects grid cell symmetry and what we can learn from it." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1635 (February 5, 2014): 20130188. http://dx.doi.org/10.1098/rstb.2013.0188.

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The mammalian hippocampal formation provides neuronal representations of environmental location but the underlying mechanisms are unclear. The majority of cells in medial entorhinal cortex and parasubiculum show spatially periodic firing patterns. Grid cells exhibit hexagonal symmetry and form an important subset of this more general class. Occasional changes between hexagonal and non-hexagonal firing patterns imply a common underlying mechanism. Importantly, the symmetrical properties are strongly affected by the geometry of the environment. Here, we introduce a field–boundary interaction model where we demonstrate that the grid cell pattern can be formed from competing place-like and boundary inputs. We show that the modelling results can accurately capture our current experimental observations.

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7

Stemmler, Martin, Alexander Mathis, and Andreas V. M. Herz. "Connecting multiple spatial scales to decode the population activity of grid cells." Science Advances 1, no. 11 (December 2015): e1500816. http://dx.doi.org/10.1126/science.1500816.

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Mammalian grid cells fire when an animal crosses the points of an imaginary hexagonal grid tessellating the environment. We show how animals can navigate by reading out a simple population vector of grid cell activity across multiple spatial scales, even though neural activity is intrinsically stochastic. This theory of dead reckoning explains why grid cells are organized into discrete modules within which all cells have the same lattice scale and orientation. The lattice scale changes from module to module and should form a geometric progression with a scale ratio of around 3/2 to minimize the risk of making large-scale errors in spatial localization. Such errors should also occur if intermediate-scale modules are silenced, whereas knocking out the module at the smallest scale will only affect spatial precision. For goal-directed navigation, the allocentric grid cell representation can be readily transformed into the egocentric goal coordinates needed for planning movements. The goal location is set by nonlinear gain fields that act on goal vector cells. This theory predicts neural and behavioral correlates of grid cell readout that transcend the known link between grid cells of the medial entorhinal cortex and place cells of the hippocampus.

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8

Schwartz, David M., and O. Ozan Koyluoglu. "On the Organization of Grid and Place Cells: Neural Denoising via Subspace Learning." Neural Computation 31, no. 8 (August 2019): 1519–50. http://dx.doi.org/10.1162/neco_a_01208.

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Place cells in the hippocampus (HC) are active when an animal visits a certain location (referred to as a place field) within an environment. Grid cells in the medial entorhinal cortex (MEC) respond at multiple locations, with firing fields that form a periodic and hexagonal tiling of the environment. The joint activity of grid and place cell populations, as a function of location, forms a neural code for space. In this article, we develop an understanding of the relationships between coding theoretically relevant properties of the combined activity of these populations and how these properties limit the robustness of this representation to noise-induced interference. These relationships are revisited by measuring the performances of biologically realizable algorithms implemented by networks of place and grid cell populations, as well as constraint neurons, which perform denoising operations. Contributions of this work include the investigation of coding theoretic limitations of the mammalian neural code for location and how communication between grid and place cell networks may improve the accuracy of each population's representation. Simulations demonstrate that denoising mechanisms analyzed here can significantly improve the fidelity of this neural representation of space. Furthermore, patterns observed in connectivity of each population of simulated cells predict that anti-Hebbian learning drives decreases in inter-HC-MEC connectivity along the dorsoventral axis.

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9

Netoff, Theoden I., Matthew I. Banks, Alan D. Dorval, Corey D. Acker, Julie S. Haas, Nancy Kopell, and John A. White. "Synchronization in Hybrid Neuronal Networks of the Hippocampal Formation." Journal of Neurophysiology 93, no. 3 (March 2005): 1197–208. http://dx.doi.org/10.1152/jn.00982.2004.

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Understanding the mechanistic bases of neuronal synchronization is a current challenge in quantitative neuroscience. We studied this problem in two putative cellular pacemakers of the mammalian hippocampal theta rhythm: glutamatergic stellate cells (SCs) of the medial entorhinal cortex and GABAergic oriens-lacunosum-moleculare (O-LM) interneurons of hippocampal region CA1. We used two experimental methods. First, we measured changes in spike timing induced by artificial synaptic inputs applied to individual neurons. We then measured responses of free-running hybrid neuronal networks, consisting of biological neurons coupled (via dynamic clamp) to biological or virtual counterparts. Results from the single-cell experiments predicted network behaviors well and are compatible with previous model-based predictions of how specific membrane mechanisms give rise to empirically measured synchronization behavior. Both cell types phase lock stably when connected via homogeneous excitatory-excitatory (E-E) or inhibitory-inhibitory (I-I) connections. Phase-locked firing is consistently synchronous for either cell type with E-E connections and nearly anti-synchronous with I-I connections. With heterogeneous connections (e.g., excitatory-inhibitory, as might be expected if members of a given population had heterogeneous connections involving intermediate interneurons), networks often settled into phase locking that was either stable or unstable, depending on the order of firing of the two cells in the hybrid network. Our results imply that excitatory SCs, but not inhibitory O-LM interneurons, are capable of synchronizing in phase via monosynaptic mutual connections of the biologically appropriate polarity. Results are largely independent of synaptic strength and synaptic kinetics, implying that our conclusions are robust and largely unaffected by synaptic plasticity.

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10

Biella, Gerardo, and Marco de Curtis. "Olfactory Inputs Activate the Medial Entorhinal Cortex Via the Hippocampus." Journal of Neurophysiology 83, no. 4 (April 1, 2000): 1924–31. http://dx.doi.org/10.1152/jn.2000.83.4.1924.

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The lateral and medial regions of the entorhinal cortex differ substantially in terms of connectivity and pattern of activation. With regard to olfactory input, a detailed and extensive physiological map of the olfactory projection to the entorhinal cortex is missing, even if anatomic studies suggest that the olfactory afferents are confined to the lateral and rostral entorhinal region. We studied the contribution of the medial and lateral entorhinal areas to olfactory processing by analyzing the responses induced by lateral olfactory tract stimulation in different entorhinal subfields of the in vitro isolated guinea pig brain. The pattern of synaptic activation of the medial and lateral entorhinal regions was reconstructed either by performing simultaneous multisite recordings or by applying current source density analysis on field potential laminar profiles obtained with 16-channel silicon probes. Current source density analysis demonstrated the existence of a direct monosynaptic olfactory input into the superficial 300 μm of the most rostral part of the lateral entorhinal cortex exclusively, whereas disynaptic sinks mediated by associative fibers arising from the piriform cortex were observed at 100–350 μm depth in the entire lateral aspect of the cortex. No local field responses were recorded in the medial entorhinal region unless a large population spike was generated in the hippocampus (dentate gyrus and CA1 region) by a stimulus 3–5× the intensity necessary to obtain a maximal monosynaptic response in the piriform cortex. In these conditions, a late sink was recorded at a depth of 600-1000 μm in the medial entorhinal area (layers III–V) 10.6 ± 0.9 (SD) msec after a population spike was simultaneously recorded in CA1. Diffuse activation of the medial entorhinal region was also obtained by repetitive low-intensity stimulation of the lateral olfactory tract at 2–8 Hz. Higher or lower stimulation frequencies did not induce hippocampal-medial entorhinal cortex activation. These results suggest that the medial and the lateral entorhinal regions have substantially different roles in processing olfactory sensory inputs.

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11

Jacob, Pierre-Yves, Tiffany Van Cauter, Bruno Poucet, Francesca Sargolini, and Etienne Save. "Medial entorhinal cortex lesions induce degradation of CA1 place cell firing stability when self-motion information is used." Brain and Neuroscience Advances 4 (January 2020): 239821282095300. http://dx.doi.org/10.1177/2398212820953004.

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The entorhinal–hippocampus network plays a central role in navigation and episodic memory formation. To investigate these interactions, we examined the effect of medial entorhinal cortex lesions on hippocampal place cell activity. Since the medial entorhinal cortex is suggested to play a role in the processing of self-motion information, we hypothesised that such processing would be necessary for maintaining stable place fields in the absence of environmental cues. Place cells were recorded as medial entorhinal cortex–lesioned rats explored a circular arena during five 16-min sessions comprising a baseline session with all sensory inputs available followed by four sessions during which environmental (i.e. visual, olfactory, tactile) cues were progressively reduced to the point that animals could rely exclusively on self-motion cues to maintain stable place fields. We found that place field stability and a number of place cell firing properties were affected by medial entorhinal cortex lesions in the baseline session. When rats were forced to rely exclusively on self-motion cues, within-session place field stability was dramatically decreased in medial entorhinal cortex rats relative to SHAM rats. These results support a major role of the medial entorhinal cortex in processing self-motion cues, with this information being conveyed to the hippocampus to help anchor and maintain a stable spatial representation during movement.

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12

van der Linden, Solange, Ferruccio Panzica, and Marco de Curtis. "Carbachol Induces Fast Oscillations in the Medial but not in the Lateral Entorhinal Cortex of the Isolated Guinea Pig Brain." Journal of Neurophysiology 82, no. 5 (November 1, 1999): 2441–50. http://dx.doi.org/10.1152/jn.1999.82.5.2441.

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Fast oscillations at 25–80 Hz (gamma activity) have been proposed to play a role in attention-related mechanisms and synaptic plasticity in cortical structures. Recently, it has been demonstrated that the preservation of the entorhinal cortex is necessary to maintain gamma oscillations in the hippocampus. Because gamma activity can be reproduced in vitro by cholinergic activation, this study examined the characteristics of gamma oscillations induced by arterial perfusion or local intracortical injections of carbachol in the entorhinal cortex of the in vitro isolated guinea pig brain preparation. Shortly after carbachol administration, fast oscillatory activity at 25.2–28.2 Hz was observed in the medial but not in the lateral entorhinal cortex. Such activity was transiently associated with oscillations in the theta range that showed a variable pattern of distribution in the entorhinal cortex. No oscillatory activity was observed when carbachol was injected in the lateral entorhinal cortex. Gamma activity in the medial entorhinal cortex showed a phase reversal at 200–400 μm, had maximal amplitude at 400–500 μm depth, and was abolished by arterial perfusion of atropine (5 μM). Local carbachol application in the medial entorhinal cortex induced gamma oscillations in the hippocampus, whereas no oscillations were observed in the amygdala and in the piriform, periamygdaloid, and perirhinal cortices ipsilateral and contralateral to the carbachol injection. Hippocampal oscillations had higher frequency than the gamma activity recorded in the entorhinal cortex, suggesting the presence of independent generators in the two structures. The selective ability of the medial but not the lateral entorhinal cortex to generate gamma activity in response to cholinergic activation suggests a differential mode of signal processing in entorhinal cortex subregions.

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Chapman, C. Andrew, and Ronald J. Racine. "Converging Inputs to the Entorhinal Cortex From the Piriform Cortex and Medial Septum: Facilitation and Current Source Density Analysis." Journal of Neurophysiology 78, no. 5 (November 1, 1997): 2602–15. http://dx.doi.org/10.1152/jn.1997.78.5.2602.

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Chapman, C. Andrew and Ronald J. Racine. Converging inputs to the entorhinal cortex from the piriform cortex and medial septum: facilitation and current source density analysis. J. Neurophysiol. 78: 2602–2615, 1997. The entorhinal cortex receives sensory inputs from the piriform cortex and modulatory inputs from the medial septum. To examine short-term synaptic facilitation effects in these pathways, current source density (CSD) analysis was used first to localize the entorhinal cortex membrane currents, which generate field potentials evoked by stimulation of these afferents. Field potentials were recorded at 50-μm intervals through the medial entorhinal cortex in urethan-anesthetized rats and the one-dimensional CSD was calculated. Piriform cortex stimulation evoked a surface-negative, deep-positive field potential component in the entorhinal cortex with mean onset and peak latencies of 10.4 and 18.4 ms. The component followed brief 100-Hz stimulation, consistent with a monosynaptic response. CSD analysis linked the component to a current sink, which often began in layer I before peaking in layer II. A later, surface-positive field potential component peaked at latencies near 45 ms and was associated with a current source in layer II. Medial septal stimulation evoked positive and negative field potential components which peaked at latencies near 7 and 16 ms, respectively. A weaker and more prolonged surface-negative, deep-positive component peaked at latencies near 25 ms. The early components were generated by currents in the hippocampal formation, and the late surface-negative component was generated by currents in layers II to IV of the entorhinal cortex. Short-term facilitation effects in conscious animals were examined using electrodes chronically implanted near layer II of the entorhinal cortex. Paired-pulse stimulation of the piriform cortex at interpulse intervals of 30 and 40 ms caused the largest facilitation (248%) of responses evoked by the second pulse. Responses evoked by medial septal stimulation also were facilitated maximally (59%) by a piriform cortex conditioning pulse delivered 30–40 ms earlier. Paired pulse stimulation of the medial septum caused the largest facilitation (149%) at intervals of 70 ms, but piriform cortex evoked responses were facilitated maximally (46%) by a septal conditioning pulse 100–200 ms earlier. Frequency potentiation effects were maximal during 12- to 18-Hz stimulation of either the piriform cortex or medial septum. Occlusion tests suggested that piriform cortex and medial septal efferents activate the same neurons. The CSD analysis results show that evoked field potential methods can be used effectively in chronically prepared animals to examine synaptic responses in the converging inputs from the piriform cortex and medial septum to the entorhinal cortex. The short-term potentiation phenomena observed here suggest that low-frequency activity in these pathways during endogenous oscillatory states may enhance entorhinal cortex responsivity to olfactory inputs.

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14

Dupret, David, and Jozsef Csicsvari. "The medial entorhinal cortex keeps Up." Nature Neuroscience 15, no. 11 (October 26, 2012): 1471–72. http://dx.doi.org/10.1038/nn.3245.

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15

Lipton, P. A., and H. Eichenbaum. "Complementary Roles of Hippocampus and Medial Entorhinal Cortex in Episodic Memory." Neural Plasticity 2008 (2008): 1–8. http://dx.doi.org/10.1155/2008/258467.

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Spatial mapping and navigation are figured prominently in the extant literature that describes hippocampal function. The medial entorhinal cortex is likewise attracting increasing interest, insofar as evidence accumulates that this area also contributes to spatial information processing. Here, we discuss recent electrophysiological findings that offer an alternate view of hippocampal and medial entorhinal function. These findings suggest complementary contributions of the hippocampus and medial entorhinal cortex in support of episodic memory, wherein hippocampal networks encode sequences of events that compose temporally and spatially extended episodes, whereas medial entorhinal networks disambiguate overlapping episodes by binding sequential events into distinct memories.

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Schmidt, Helene, Anjali Gour, Jakob Straehle, Kevin M. Boergens, Michael Brecht, and Moritz Helmstaedter. "Axonal synapse sorting in medial entorhinal cortex." Nature 549, no. 7673 (September 2017): 469–75. http://dx.doi.org/10.1038/nature24005.

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Kropff, Emilio, James E. Carmichael, May-Britt Moser, and Edvard I. Moser. "Speed cells in the medial entorhinal cortex." Nature 523, no. 7561 (July 2015): 419–24. http://dx.doi.org/10.1038/nature14622.

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Schmidt-Hieber, Christoph, and Michael Häusser. "How to build a grid cell." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1635 (February 5, 2014): 20120520. http://dx.doi.org/10.1098/rstb.2012.0520.

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Neurons in the medial entorhinal cortex fire action potentials at regular spatial intervals, creating a striking grid-like pattern of spike rates spanning the whole environment of a navigating animal. This remarkable spatial code may represent a neural map for path integration. Recent advances using patch-clamp recordings from entorhinal cortex neurons in vitro and in vivo have revealed how the microcircuitry in the medial entorhinal cortex may contribute to grid cell firing patterns, and how grid cells may transform synaptic inputs into spike output during firing field crossings. These new findings provide key insights into the ingredients necessary to build a grid cell.

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Hasselmo, Michael E. "Neuronal rebound spiking, resonance frequency and theta cycle skipping may contribute to grid cell firing in medial entorhinal cortex." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1635 (February 5, 2014): 20120523. http://dx.doi.org/10.1098/rstb.2012.0523.

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Data show a relationship of cellular resonance and network oscillations in the entorhinal cortex to the spatial periodicity of grid cells. This paper presents a model that simulates the resonance and rebound spiking properties of entorhinal neurons to generate spatial periodicity dependent upon phasic input from medial septum. The model shows that a difference in spatial periodicity can result from a difference in neuronal resonance frequency that replicates data from several experiments. The model also demonstrates a functional role for the phenomenon of theta cycle skipping in the medial entorhinal cortex.

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Canto, Cathrin B., and Menno P. Witter. "Cellular properties of principal neurons in the rat entorhinal cortex. II. The medial entorhinal cortex." Hippocampus 22, no. 6 (December 7, 2011): 1277–99. http://dx.doi.org/10.1002/hipo.20993.

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Høydal, Øyvind Arne, Emilie Ranheim Skytøen, Sebastian Ola Andersson, May-Britt Moser, and Edvard I. Moser. "Object-vector coding in the medial entorhinal cortex." Nature 568, no. 7752 (April 2019): 400–404. http://dx.doi.org/10.1038/s41586-019-1077-7.

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Hinman, James R., Mark P. Brandon, Jason R. Climer, G. William Chapman, and Michael E. Hasselmo. "Multiple Running Speed Signals in Medial Entorhinal Cortex." Neuron 91, no. 3 (August 2016): 666–79. http://dx.doi.org/10.1016/j.neuron.2016.06.027.

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Diehl, Geoffrey W., Olivia J. Hon, Stefan Leutgeb, and Jill K. Leutgeb. "Stability of medial entorhinal cortex representations over time." Hippocampus 29, no. 3 (September 2, 2018): 284–302. http://dx.doi.org/10.1002/hipo.23017.

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Scharfman, H. E. "Hyperexcitability of entorhinal cortex and hippocampus after application of aminooxyacetic acid (AOAA) to layer III of the rat medial entorhinal cortex in vitro." Journal of Neurophysiology 76, no. 5 (November 1, 1996): 2986–3001. http://dx.doi.org/10.1152/jn.1996.76.5.2986.

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1. Injection of aminooxyacetic acid (AOAA) into the entorhinal cortex in vivo produces acute seizures and cell loss in medial entorhinal cortex. To understand these effects, AOAA was applied directly to the medial entorhinal cortex in slices containing both the entorhinal cortex and hippocampus. Extracellular and intracellular recordings were made in both the entorhinal cortex and hippocampus to study responses to angular bundle stimulation and spontaneous activity. 2. AOAA was applied focally by leak from a micropipette or by pressure ejection. Evoked potentials increased gradually within 5 min of application, particularly the late, negative components. Evoked potentials continued to increase for up to 1 h, and these changes persisted for the remainder of the experiment (up to 5 h after drug application). 3. Paired pulse facilitation (100-ms interval) was also enhanced after AOAA application. Increasing stimulus frequency to 1-10 Hz increased evoked potentials further, and after several seconds of such stimulation multiple field potentials occurred. When stimulation was stopped at this point, repetitive field potentials occurred spontaneously for 1-2 min. These recordings, and simultaneous extracellular recordings in different layers, indicated that spontaneous synchronous activity occurred in entorhinal neurons. Intracellularly labeled cortical pyramidal cells depolarized and discharged during spontaneous and evoked field potentials. 4. The effects of AOAA were blocked reversibly by bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-amino-5-phosphonovalerate (D-APV; 25 microM) or focal application of D-APV to the medial entorhinal cortex. 5. Simultaneous extracellular recordings from the entorhinal cortex and hippocampus demonstrated that spontaneous synchronous activity in layer III was often followed within several milliseconds by negative field potentials in the terminal zones of the perforant path (stratum moleculare of the dentate gyrus and stratum lacunosum-moleculare of area CA1). The extracellular potentials recorded in the dentate gyrus corresponded to excitatory postsynaptic potentials and action potentials in dentate granule cells. However, extracellular potentials in area CA1 were small and rarely correlated with discharge in CA1 pyramidal cells. 6. The results demonstrate that AOAA application leads to an NMDA-receptor-dependent enhancement of evoked potentials in medial entorhinal cortical neurons, which appears to be irreversible. The potentials can be facilitated by repetitive stimulation, and lead to synchronized discharges of entorhinal neurons. The discharges invade other areas such as the hippocampus, indicating how seizure activity may spread after AOAA injection in vivo. These data suggest that AOAA may be a useful tool to study longlasting changes in NMDA receptor function that lead to epileptiform activity and neurodegeneration.

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Heys, James G., Lisa M. Giocomo, and Michael E. Hasselmo. "Cholinergic Modulation of the Resonance Properties of Stellate Cells in Layer II of Medial Entorhinal Cortex." Journal of Neurophysiology 104, no. 1 (July 2010): 258–70. http://dx.doi.org/10.1152/jn.00492.2009.

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In vitro whole cell patch-clamp recordings of stellate cells in layer II of medial entorhinal cortex show a subthreshold membrane potential resonance in response to a sinusoidal current injection of varying frequency. Physiological recordings from awake behaving animals show that neurons in layer II medial entorhinal cortex, termed “grid cells,” fire in a spatially selective manner such that each cell's multiple firing fields form a hexagonal grid. Both the spatial periodicity of the grid fields and the resonance frequency change systematically in neurons along the dorsal to ventral axis of medial entorhinal cortex. Previous work has also shown that grid field spacing and acetylcholine levels change as a function of the novelty to a particular environment. Using in vitro whole cell patch-clamp recordings, our study shows that both resonance frequency and resonance strength vary as a function of cholinergic modulation. Furthermore, our data suggest that these changes in resonance properties are mediated through modulation of h-current and m-current.

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Kinnavane, Lisa, Eman Amin, Cristian M. Olarte-Sánchez, and John P. Aggleton. "Medial temporal pathways for contextual learning: Network c-fos mapping in rats with or without perirhinal cortex lesions." Brain and Neuroscience Advances 1 (January 1, 2017): 239821281769416. http://dx.doi.org/10.1177/2398212817694167.

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Background: In the rat brain, context information is thought to engage network interactions between the postrhinal cortex, medial entorhinal cortex, and the hippocampus. In contrast, object information is thought to be more reliant on perirhinal cortex and lateral entorhinal cortex interactions with the hippocampus. Method: The ‘context network’ was explored by mapping expression of the immediate-early gene, c- fos, after exposure to a new spatial environment. Results: Structural equation modelling of Fos counts produced networks of good fit that closely matched prior predictions based on anatomically grounded functional models. These same models did not, however, fit the Fos data from home-cage controls nor did they fit the corresponding data from a previous study exploring object recognition. These additional analyses highlight the specificity of the context network. The home-cage controls, meanwhile, showed raised levels of inter-area Fos correlations between the many sites examined, that is, their changes in Fos levels lacked anatomical specificity. A total of two additional groups of rats received perirhinal cortex lesions. While the loss of perirhinal cortex reduced lateral entorhinal c- fos expression, it did not affect mean levels of hippocampal c- fos expression. Similarly, overall c- fos expression in the prelimbic cortex, retrosplenial cortex, and nucleus reuniens of the thalamus appeared unaffected by the perirhinal cortex lesions. Conclusion: The perirhinal cortex lesions disrupted network interactions involving the medial entorhinal cortex and the hippocampus, highlighting ways in which perirhinal cortex might affect specific aspects of context learning.

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Biella, Gerardo, Paolo Spaiardi, Mauro Toselli, Marco de Curtis, and Vadym Gnatkovsky. "Functional Interactions Within the Parahippocampal Region Revealed by Voltage-Sensitive Dye Imaging in the Isolated Guinea Pig Brain." Journal of Neurophysiology 103, no. 2 (February 2010): 725–32. http://dx.doi.org/10.1152/jn.00722.2009.

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The massive transfer of information from the neocortex to the entorhinal cortex (and vice versa) is hindered by a powerful inhibitory control generated in the perirhinal cortex. In vivo and in vitro experiments performed in rodents and cats support this conclusion, further extended in the present study to the analysis of the interaction between the entorhinal cortex and other parahippocampal areas, such as the postrhinal and the retrosplenial cortices. The experiments were performed in the in vitro isolated guinea pig brain by a combined approach based on electrophysiological recordings and fast imaging of optical signals generated by voltage-sensitive dyes applied to the entire brain by arterial perfusion. Local stimuli delivered in different portions of the perirhinal, postrhinal, and retrosplenial cortex evoked local responses that did not propagate to the entorhinal cortex. Neither high- and low-frequency-patterned stimulation nor paired associative stimuli facilitated the propagation of activity to the entorhinal region. Similar stimulations performed during cholinergic neuromodulation with carbachol were also ineffective in overcoming the inhibitory network that controls propagation to the entorhinal cortex. The pharmacological inactivation of GABAergic transmission by local application of bicuculline (1 mM) in area 36 of the perirhinal cortex facilitated the longitudinal (rostrocaudal) propagation of activity into the perirhinal/postrhinal cortices but did not cause propagation into the entorhinal cortex. Bicuculline injection in both area 35 and medial entorhinal cortex released the inhibitory control and allowed the propagation of the neural activity to the entorhinal cortex. These results demonstrate that, as for the perirhinal-entorhinal reciprocal interactions, also the connections between the postrhinal/retrosplenial cortices and the entorhinal region are subject to a powerful inhibitory control.

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GUANELLA, ALEXIS, DANIEL KIPER, and PAUL VERSCHURE. "A MODEL OF GRID CELLS BASED ON A TWISTED TORUS TOPOLOGY." International Journal of Neural Systems 17, no. 04 (August 2007): 231–40. http://dx.doi.org/10.1142/s0129065707001093.

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The grid cells of the rat medial entorhinal cortex (MEC) show an increased firing frequency when the position of the animal correlates with multiple regions of the environment that are arranged in regular triangular grids. Here, we describe an artificial neural network based on a twisted torus topology, which allows for the generation of regular triangular grids. The association of the activity of pre-defined hippocampal place cells with entorhinal grid cells allows for a highly robust-to-noise calibration mechanism, suggesting a role for the hippocampal back-projections to the entorhinal cortex.

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Giocomo, Lisa M., Tor Stensola, Tora Bonnevie, Tiffany Van Cauter, May-Britt Moser, and Edvard I. Moser. "Topography of Head Direction Cells in Medial Entorhinal Cortex." Current Biology 24, no. 3 (February 2014): 252–62. http://dx.doi.org/10.1016/j.cub.2013.12.002.

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Sasaki, Takuya, Stefan Leutgeb, and Jill K. Leutgeb. "Spatial and memory circuits in the medial entorhinal cortex." Current Opinion in Neurobiology 32 (June 2015): 16–23. http://dx.doi.org/10.1016/j.conb.2014.10.008.

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Powers, Alice Schade. "Relevance of medial and dorsal cortex function to the dorsalization hypothesis." Behavioral and Brain Sciences 26, no. 5 (October 2003): 566–67. http://dx.doi.org/10.1017/s0140525x03360121.

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The overall dorsalizing effect proposed by the authors may be consistent with behavioral evidence showing that the dorsal cortex of reptiles functions like the hippocampal formation of mammals. It is suggested that the dorsal cortex of reptiles expanded in this dorsalizing process to become both entorhinal/subicular cortex and sensory neocortex.

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Scharfman, H. E., J. H. Goodman, F. Du, and R. Schwarcz. "Chronic Changes in Synaptic Responses of Entorhinal and Hippocampal Neurons After Amino-Oxyacetic Acid (AOAA)–Induced Entorhinal Cortical Neuron Loss." Journal of Neurophysiology 80, no. 6 (December 1, 1998): 3031–46. http://dx.doi.org/10.1152/jn.1998.80.6.3031.

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Scharfman, H. E., J. H. Goodman, F. Du, and R. Schwarcz. Chronic changes in synaptic responses of entorhinal and hippocampal neurons after amino-oxyacetic acid (AOAA)–induced entorhinal neuron loss. J. Neurophysiol. 80: 3031–3046, 1998. Synaptic responses of entorhinal cortical and hippocampal neurons were examined in vivo and in vitro, 1 mo to 1.5 yr after a unilateral entorhinal lesion caused by a focal injection of amino-oxyacetic acid (AOAA). It has been shown previously that injection of AOAA into the medial entorhinal cortex produces cell loss in layer III preferentially. Although behavioral seizures stopped ∼2 h after AOAA treatment, abnormal evoked responses were recorded as long as 1.5 yr later in the entorhinal cortex and hippocampus. In the majority of slices from AOAA-treated rats, responses recorded in the superficial layers of the medial entorhinal cortex to white matter, presubiculum, or parasubiculum stimulation were abnormal. Extracellularly recorded responses to white matter stimulation were prolonged and repetitive in the superficial layers. Intracellular recordings showed that residual principal cells in superficial layers produced prolonged, repetitive excitatory postsynaptic potentials (EPSPs) and discharges in response to white matter stimulation compared with brief EPSPs and a single discharge in controls. Responses of deep layer neurons of AOAA-treated rats did not differ from controls in their initial synaptic response. However, in a some of these neurons, additional periods of excitatory activity occurred after a delay. Abnormal responses were recorded from slices ipsilateral as well as contralateral to the lesioned hemisphere. Recordings from the entorhinal cortex in vivo were abnormal also, as demonstrated by prolonged and repetitive responses to stimulation of the area CA1/subiculum border. Evoked responses of hippocampal neurons, recorded in vitro or in vivo, demonstrated abnormalities in selected pathways, such as responses of CA3 neurons to hilar stimulation in vitro. There was a deficit in the duration of potentiation of CA1 population spikes in response to repetitive CA3 stimulation in AOAA-treated rats. Theta activity was reduced in amplitude in area CA1 and the dentate gyrus of AOAA-treated rats, although evoked responses to angular bundle stimulation could not be distinguished from controls. The results demonstrate that a preferential lesion of layer III of the entorhinal cortex produces a long-lasting change in evoked and spontaneous activity in parts of the entorhinal cortex and hippocampus. Given the similarity of the lesion produced by AOAA and entorhinal lesions in temporal lobe epileptics, these data support the hypothesis that preferential damage to the entorhinal cortex contributes to long-lasting changes in excitability, which could be relevant to the etiology of temporal lobe epilepsy.

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Butler, William N., Kiah Hardcastle, and Lisa M. Giocomo. "Remembered reward locations restructure entorhinal spatial maps." Science 363, no. 6434 (March 28, 2019): 1447–52. http://dx.doi.org/10.1126/science.aav5297.

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Ethologically relevant navigational strategies often incorporate remembered reward locations. Although neurons in the medial entorhinal cortex provide a maplike representation of the external spatial world, whether this map integrates information regarding learned reward locations remains unknown. We compared entorhinal coding in rats during a free-foraging task and a spatial memory task. Entorhinal spatial maps restructured to incorporate a learned reward location, which in turn improved positional decoding near this location. This finding indicates that different navigational strategies drive the emergence of discrete entorhinal maps of space and points to a role for entorhinal codes in a diverse range of navigational behaviors.

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Dias, Marcelo, Raquel Ferreira, and Miguel Remondes. "Medial Entorhinal Cortex Excitatory Neurons Are Necessary for Accurate Timing." Journal of Neuroscience 41, no. 48 (October 20, 2021): 9932–43. http://dx.doi.org/10.1523/jneurosci.0750-21.2021.

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Schmidt-Hieber, Christoph, and Michael Häusser. "Cellular mechanisms of spatial navigation in the medial entorhinal cortex." Nature Neuroscience 16, no. 3 (February 10, 2013): 325–31. http://dx.doi.org/10.1038/nn.3340.

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36

Tsuno, Yusuke, George W. Chapman, and Michael E. Hasselmo. "Rebound spiking properties of mouse medial entorhinal cortex neuronsin vivo." European Journal of Neuroscience 42, no. 11 (November 17, 2015): 2974–84. http://dx.doi.org/10.1111/ejn.13097.

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Martínez, Joan José, Bahar Rahsepar, and John A. White. "Anatomical and Electrophysiological Clustering of Superficial Medial Entorhinal Cortex Interneurons." eneuro 4, no. 5 (September 2017): ENEURO.0263–16.2017. http://dx.doi.org/10.1523/eneuro.0263-16.2017.

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Naumann, Robert K., Patricia Preston-Ferrer, Michael Brecht, and Andrea Burgalossi. "Structural modularity and grid activity in the medial entorhinal cortex." Journal of Neurophysiology 119, no. 6 (June 1, 2018): 2129–44. http://dx.doi.org/10.1152/jn.00574.2017.

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Following the groundbreaking discovery of grid cells, the medial entorhinal cortex (MEC) has become the focus of intense anatomical, physiological, and computational investigations. Whether and how grid activity maps onto cell types and cortical architecture is still an open question. Fundamental similarities in microcircuits, function, and connectivity suggest a homology between rodent MEC and human posteromedial entorhinal cortex. Both are specialized for spatial processing and display similar cellular organization, consisting of layer 2 pyramidal/calbindin cell patches superimposed on scattered stellate neurons. Recent data indicate the existence of a further nonoverlapping modular system (zinc patches) within the superficial MEC layers. Zinc and calbindin patches have been shown to receive largely segregated inputs from the presubiculum and parasubiculum. Grid cells are also clustered in the MEC, and we discuss possible structure-function schemes on how grid activity could map onto cortical patch systems. We hypothesize that in the superficial layers of the MEC, anatomical location can be predictive of function; thus relating functional properties and neuronal morphologies to the cortical modules will be necessary for resolving how grid activity maps onto cortical architecture. Imaging or cell identification approaches in freely moving animals will be required for testing this hypothesis.

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Dickson, C. T., A. R. Mena, and A. Alonso. "Electroresponsiveness of medial entorhinal cortex layer III neurons in vitro." Neuroscience 81, no. 4 (October 1997): 937–50. http://dx.doi.org/10.1016/s0306-4522(97)00263-7.

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Miao, Chenglin, Qichen Cao, Hiroshi T. Ito, Homare Yamahachi, Menno P. Witter, May-Britt Moser, and Edvard I. Moser. "Hippocampal Remapping after Partial Inactivation of the Medial Entorhinal Cortex." Neuron 88, no. 3 (November 2015): 590–603. http://dx.doi.org/10.1016/j.neuron.2015.09.051.

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Robinson, Nick T. M., James B. Priestley, Jon W. Rueckemann, Aaron D. Garcia, Vittoria A. Smeglin, Francesca A. Marino, and Howard Eichenbaum. "Medial Entorhinal Cortex Selectively Supports Temporal Coding by Hippocampal Neurons." Neuron 94, no. 3 (May 2017): 677–88. http://dx.doi.org/10.1016/j.neuron.2017.04.003.

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42

White, John A., Angel Alonso, and Alan R. Kay. "A heart-like Na+ current in the medial entorhinal cortex." Neuron 11, no. 6 (December 1993): 1037–47. http://dx.doi.org/10.1016/0896-6273(93)90217-f.

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43

Winterer, Jochen, Nikolaus Maier, Christian Wozny, Prateep Beed, Jörg Breustedt, Roberta Evangelista, Yangfan Peng, Tiziano D’Albis, Richard Kempter, and Dietmar Schmitz. "Excitatory Microcircuits within Superficial Layers of the Medial Entorhinal Cortex." Cell Reports 19, no. 6 (May 2017): 1110–16. http://dx.doi.org/10.1016/j.celrep.2017.04.041.

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44

Bilgel, Murat, Jacob Ziontz, Andrea Shafer, Luigi Ferrucci, Dean Wong, and Susan Resnick. "Medial Temporal Tau Pathology Is Associated With Verbal Memory." Innovation in Aging 4, Supplement_1 (December 1, 2020): 767. http://dx.doi.org/10.1093/geroni/igaa057.2770.

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Abstract Medial temporal tau pathology is frequently observed in individuals over 70 regardless of cognitive status. To understand the link between tau and cognitive performance, we evaluated tau pathology using 18F-flortaucipir positron emission tomography among 95 cognitively normal participants from the Baltimore Longitudinal Study of Aging. We examined tau levels in early Braak regions (entorhinal cortex and hippocampus) in relation to verbal episodic memory performance concurrent with and prior to the tau scan using linear mixed effects models adjusted for age, sex, amyloid status, and time from PET scan. Higher hippocampal tau burden had a trend-level association with lower concurrent memory performance (p=0.05). Greater tau pathology in the hippocampus and entorhinal cortex was associated with steeper decline in memory performance prior to tau scan (p=0.013 and 0.026, respectively). These findings suggest that therapeutic interventions targeting tau pathology may need to be administered early among cognitively normal individuals to prevent memory decline.

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Lowe, Val J., Tyler J. Bruinsma, Heather J. Wiste, Hoon-Ki Min, Stephen D. Weigand, Ping Fang, Matthew L. Senjem, et al. "Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults." Neurology 93, no. 1 (May 30, 2019): e29-e39. http://dx.doi.org/10.1212/wnl.0000000000007728.

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ObjectiveTo assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults.MethodsTau- and amyloid-PET were performed in 579 CU participants aged 50–98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A−) and normal/abnormal regional tau-PET (T+/T−). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30–49.ResultsHigher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A− and A+.ConclusionsTau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.

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Solstad, Trygve, Charlotte N. Boccara, Emilio Kropff, May-Britt Moser, and Edvard I. Moser. "Representation of Geometric Borders in the Entorhinal Cortex." Science 322, no. 5909 (December 19, 2008): 1865–68. http://dx.doi.org/10.1126/science.1166466.

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We report the existence of an entorhinal cell type that fires when an animal is close to the borders of the proximal environment. The orientation-specific edge-apposing activity of these “border cells” is maintained when the environment is stretched and during testing in enclosures of different size and shape in different rooms. Border cells are relatively sparse, making up less than 10% of the local cell population, but can be found in all layers of the medial entorhinal cortex as well as the adjacent parasubiculum, often intermingled with head-direction cells and grid cells. Border cells may be instrumental in planning trajectories and anchoring grid fields and place fields to a geometric reference frame.

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Jacob, Pierre-Yves, Marta Gordillo-Salas, Justine Facchini, Bruno Poucet, Etienne Save, and Francesca Sargolini. "Medial entorhinal cortex and medial septum contribute to self-motion-based linear distance estimation." Brain Structure and Function 222, no. 6 (February 4, 2017): 2727–42. http://dx.doi.org/10.1007/s00429-017-1368-4.

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Gonzalez-Sulser, A., D. Parthier, A. Candela, C. McClure, H. Pastoll, D. Garden, G. Surmeli, and M. F. Nolan. "GABAergic Projections from the Medial Septum Selectively Inhibit Interneurons in the Medial Entorhinal Cortex." Journal of Neuroscience 34, no. 50 (December 10, 2014): 16739–43. http://dx.doi.org/10.1523/jneurosci.1612-14.2014.

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Lipton, P. A., J. A. White, and H. Eichenbaum. "Disambiguation of Overlapping Experiences by Neurons in the Medial Entorhinal Cortex." Journal of Neuroscience 27, no. 21 (May 23, 2007): 5787–95. http://dx.doi.org/10.1523/jneurosci.1063-07.2007.

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Van Cauter, T., J. Camon, A. Alvernhe, C. Elduayen, F. Sargolini, and E. Save. "Distinct Roles of Medial and Lateral Entorhinal Cortex in Spatial Cognition." Cerebral Cortex 23, no. 2 (February 22, 2012): 451–59. http://dx.doi.org/10.1093/cercor/bhs033.

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