The Experts below are selected from a list of 4518 Experts worldwide ranked by ideXlab platform
Edvard I. Moser - One of the best experts on this subject based on the ideXlab platform.
-
A Brainstem Locomotor Circuit Drives the Activity of Speed Cells in the Medial Entorhinal Cortex.
Cell Reports, 2020Co-Authors: Miguel M. Carvalho, Maybritt Moser, Emilio Kropff, Menno P. Witter, Nouk Tanke, Edvard I. MoserAbstract:Summary Locomotion activates an array of sensory inputs that may help build the self-position map of the Medial Entorhinal Cortex (MEC). In this map, speed-coding neurons are thought to dynamically update representations of the animal’s position. A possible origin for the Entorhinal speed signal is the mesencephalic locomotor region (MLR), which is critically involved in the activation of locomotor programs. Here, we describe, in rats, a circuit connecting the pedunculopontine tegmental nucleus (PPN) of the MLR to the MEC via the horizontal limb of the diagonal band of Broca (HDB). At each level of this pathway, locomotion speed is linearly encoded in neuronal firing rates. Optogenetic activation of PPN cells drives locomotion and modulates activity of speed-modulated neurons in HDB and MEC. Our results provide evidence for a pathway by which brainstem speed signals can reach cortical structures implicated in navigation and higher-order dynamic representations of space.
-
Object-vector coding in the Medial Entorhinal Cortex
Nature, 2019Co-Authors: Oyvind Arne Hoydal, Emilie Ranheim Skytoen, Maybritt Moser, Sebastian Ola Andersson, Edvard I. MoserAbstract:The hippocampus and the Medial Entorhinal Cortex are part of a brain system that maps self-location during navigation in the proximal environment1,2. In this system, correlations between neural firing and an animal’s position or orientation are so evident that cell types have been given simple descriptive names, such as place cells3, grid cells4, border cells5,6 and head-direction cells7. While the number of identified functional cell types is growing at a steady rate, insights remain limited by an almost-exclusive reliance on recordings from rodents foraging in empty enclosures that are different from the richly populated, geometrically irregular environments of the natural world. In environments that contain discrete objects, animals are known to store information about distance and direction to those objects and to use this vector information to guide navigation8–10. Theoretical studies have proposed that such vector operations are supported by neurons that use distance and direction from discrete objects11,12 or boundaries13,14 to determine the animal’s location, but—although some cells with vector-coding properties may be present in the hippocampus15 and subiculum16,17—it remains to be determined whether and how vectorial operations are implemented in the wider neural representation of space. Here we show that a large fraction of Medial Entorhinal Cortex neurons fire specifically when mice are at given distances and directions from spatially confined objects. These ‘object-vector cells’ are tuned equally to a spectrum of discrete objects, irrespective of their location in the test arena, as well as to a broad range of dimensions and shapes, from point-like objects to extended surfaces. Our findings point to vector coding as a predominant form of position coding in the Medial Entorhinal Cortex. Cells in the mouse Medial Entorhinal Cortex that fire when mice are at a specific distance and direction from a stationary object suggest that vector coding is important for rodent navigation.
-
functional properties of stellate cells in Medial Entorhinal Cortex layer ii
eLife, 2018Co-Authors: David C Rowland, Horstandreas Obenhaus, Emilie Ranheim Skytoen, Qiangwei Zhang, Clifford G Kentros, Edvard I. Moser, Maybritt MoserAbstract:: 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.
-
functional properties of stellate cells in Medial Entorhinal Cortex layer ii
eLife, 2018Co-Authors: David C Rowland, Horstandreas Obenhaus, Emilie Ranheim Skytoen, Qiangwei Zhang, Clifford G Kentros, Edvard I. Moser, Maybritt MoserAbstract:: 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.
-
Object-vector coding in the Medial Entorhinal Cortex
2018Co-Authors: Oyvind Arne Hoydal, Emilie Ranheim Skytoen, Maybritt Moser, Edvard I. MoserAbstract:Mammals use distances and directions from local objects to calculate trajectories during navigation but how such vectorial operations are implemented in neural representations of space has not been determined. Here we show in freely moving mice that a population of neurons in the Medial Entorhinal Cortex (MEC) responds specifically when the animal is at a given distance and direction from a spatially confined object. These "object-vector cells" are tuned similarly to a spectrum of discrete objects, irrespective of their location in the test arena. The vector relationships are expressed from the outset in novel environments with novel objects. Object-vector cells are distinct from grid cells, which use a distal reference frame, but the cells exhibit some mixed selectivity with head-direction and border cells. Collectively, these observations show that object locations are integrated in metric representations of self-location, with specific subsets of MEC neurons encoding vector relationships to individual objects.
Dietmar Schmitz - One of the best experts on this subject based on the ideXlab platform.
-
Excitatory microcircuits within superficial layers of the Medial Entorhinal Cortex
Cell Reports, 2017Co-Authors: Jochen Winterer, Prateep Beed, Nikolaus Maier, Christian Wozny, Jörg Breustedt, Roberta Evangelista, Yangfan Peng, Tiziano D'albis, Richard Kempter, Dietmar SchmitzAbstract:The distinctive firing pattern of grid cells in the Medial Entorhinal Cortex (MEC) supports its role in the representation of space. It is widely believed that the hexagonal firing field of grid cells emerges from neural dynamics that depend on the local microcircuitry. However, local networks within the MEC are still not sufficiently characterized. Here, applying up to eight simultaneous whole-cell recordings in acute brain slices, we demonstrate the existence of unitary excitatory connections between principal neurons in the superficial layers of the MEC. In particular, we find prevalent feed-forward excitation from pyramidal neurons in layer III and layer II onto stellate cells in layer II, which might contribute to the generation or the inheritance of grid cell patterns.
-
Anatomical Organization and Spatiotemporal Firing Patterns of Layer 3 Neurons in the Rat Medial Entorhinal Cortex.
Journal of Neuroscience, 2015Co-Authors: Qiusong Tang, Saikat Ray, Robert K. Naumann, Patricia Preston-ferrer, Christian Laut Ebbesen, Juan I. Sanguinetti-scheck, Anja Gundlfinger, Jochen Winterer, Prateep Beed, Dietmar SchmitzAbstract:Layer 3 of the Medial Entorhinal Cortex is a major gateway from the neoCortex to the hippocampus. Here we addressed structure-function relationships in Medial Entorhinal Cortex layer 3 by combining anatomical analysis with juxtacellular identification of single neurons in freely behaving rats. Anatomically, layer 3 appears as a relatively homogeneous cell sheet. Dual-retrograde neuronal tracing experiments indicate a large overlap between layer 3 pyramidal populations, which project to ipsilateral hippocampus, and the contralateral Medial Entorhinal Cortex. These cells were intermingled within layer 3, and had similar morphological and intrinsic electrophysiological properties. Dendritic trees of layer 3 neurons largely avoided the calbindin-positive patches in layer 2. Identification of layer 3 neurons during spatial exploration (n = 17) and extracellular recordings (n = 52) pointed to homogeneous spatial discharge patterns. Layer 3 neurons showed only weak spiking theta rhythmicity and sparse head-direction selectivity. A majority of cells (50 of 69) showed no significant spatial modulation. All of the ∼28% of neurons that carried significant amounts of spatial information (19 of 69) discharged in irregular spatial patterns. Thus, layer 3 spatiotemporal firing properties are remarkably different from those of layer 2, where theta rhythmicity is prominent and spatially modulated cells often discharge in grid or border patterns. Significance statement: Neurons within the superficial layers of the Medial Entorhinal Cortex (MEC) often discharge in border, head-direction, and theta-modulated grid patterns. It is still largely unknown how defined discharge patterns relate to cellular diversity in the superficial layers of the MEC. In the present study, we addressed this issue by combining anatomical analysis with juxtacellular identification of single layer 3 neurons in freely behaving rats. We provide evidence that the anatomical organization and spatiotemporal firing properties of layer 3 neurons are remarkably different from those in layer 2. Specifically, most layer 3 neurons discharged in spatially irregular firing patterns, with weak theta-modulation and head-directional selectivity. This work thus poses constraints on the spatiotemporal patterns reaching downstream targets, like the hippocampus.
-
Inhibitory Gradient along the Dorsoventral Axis in the Medial Entorhinal Cortex
Neuron, 2013Co-Authors: Prateep Beed, Michael Brecht, Andrea Burgalossi, Anja Gundlfinger, Sophie Schneiderbauer, Jie Song, Claudia Böhm, Imre Vida, Dietmar SchmitzAbstract:Local inhibitory microcircuits in the Medial Entorhinal Cortex (MEC) and their role in network activity are little investigated. Using a combination of electrophysiological, optical, and morphological circuit analysis tools, we find that layer II stellate cells are embedded in a dense local inhibitory microcircuit. Specifically, we report a gradient of inhibitory inputs along the dorsoventral axis of the MEC, with the majority of this local inhibition arising from parvalbumin positive (PV+) interneurons. Finally, the gradient of PV+ fibers is accompanied by a gradient in the power of extracellular network oscillations in the gamma range, measured both in vitro and in vivo. The reported differences in the inhibitory microcircuitry in layer II of the MEC may therefore have a profound functional impact on the computational working principles at different locations of the Entorhinal network and influence the input pathways to the hippocampus.
-
Analysis of Excitatory Microcircuitry in the Medial Entorhinal Cortex Reveals Cell-Type-Specific Differences
Neuron, 2010Co-Authors: Prateep Beed, Michael H. K. Bendels, Christian Leibold, Hauke F. Wiegand, Friedrich W. Johenning, Dietmar SchmitzAbstract:Medial Entorhinal Cortex (MEC) plays an important role in physiological processes underlying navigation, learning, and memory. Excitatory cells in the different MEC layers project in a region-specific manner to the hippocampus. However, the intrinsic microcircuitry of the main excitatory cells in the superficial MEC layers is largely unknown. Using scanning photostimulation, we investigated the functional microcircuitry of two such cell types, stellate and pyramidal cells. We found cell-type-specific intralaminar and ascending interlaminar feedback inputs. The ascending interlaminar inputs display distinct organizational principles depending on the cell-type and its position within the superficial lamina: the spatial spread of inputs for stellate cells is narrower than for pyramidal cells, while inputs to pyramidal cells in layer 3, but not in layer 2, exhibit an asymmetric offset to the Medial side of the cell's main axis. Differential laminar sources of excitatory inputs might contribute to the functional diversity of stellate and pyramidal cells.
-
dopamine suppresses stimulus induced field potentials in layer iii of rat Medial Entorhinal Cortex
Neuroscience Letters, 1998Co-Authors: Kerstin Stenkamp, Uwe Heinemann, Dietmar SchmitzAbstract:Abstract We studied the effect of dopamine (DA) on field potential responses in layer III of the Medial Entorhinal Cortex (mEC) evoked by synaptic stimulation of superficial layers of the lateral EC either by single or paired-pulses. The maximum amplitude of the field response was reduced to 50.6±2.6% by DA (500 μ M) bath-applied for 5 min. Both the D1 antagonist SCH 23390 (20 μ M) and the D2 antagonist sulpiride (20–50 μ M) reduced the effect of DA to the same extent, namely 18% less reduction in their presence. The D2 agonist quinelorane (500 μ M) reduced the field response to 75±4.0%, whereas the D1 agonist SKF38393 was without significant effect. The paired-pulse ratio increased significantly during DA application. These results suggest predominant D2 receptor involvement in the decrement of synaptic transmission in layer III by dopamine. Paired-pulse experiments may be indicative of a presynaptic mechanism of action.
Michael E. Hasselmo - One of the best experts on this subject based on the ideXlab platform.
-
Multiple Running Speed Signals in Medial Entorhinal Cortex.
Neuron, 2016Co-Authors: James R. Hinman, Mark P. Brandon, Jason R. Climer, G. William Chapman, Michael E. HasselmoAbstract:Grid cells in Medial Entorhinal Cortex (MEC) can be modeled using oscillatory interference or attractor dynamic mechanisms that perform path integration, a computation requiring information about running direction and speed. The two classes of computational models often use either an oscillatory frequency or a firing rate that increases as a function of running speed. Yet it is currently not known whether these are two manifestations of the same speed signal or dissociable signals with potentially different anatomical substrates. We examined coding of running speed in MEC and identified these two speed signals to be independent of each other within individual neurons. The Medial septum (MS) is strongly linked to locomotor behavior, and removal of MS input resulted in strengthening of the firing rate speed signal, while decreasing the strength of the oscillatory speed signal. Thus, two speed signals are present in MEC that are differentially affected by disrupted MS input.
-
Rebound spiking properties of mouse Medial Entorhinal Cortex neurons in vivo.
European Journal of Neuroscience, 2015Co-Authors: Yusuke Tsuno, George W. Chapman, Michael E. HasselmoAbstract:The Medial Entorhinal Cortex is the gateway between the Cortex and hippocampus, and plays a critical role in spatial coding as represented by grid cell activity. In the Medial Entorhinal Cortex, inhibitory circuits are robust, and the presence of the h-current leads to rebound potentials and rebound spiking in in vitro experiments. It has been hypothesized that these properties, combined with network oscillations, may contribute to grid cell formation. To examine the properties of in vivo rebound spikes, we performed whole-cell patch-clamp recordings in Medial Entorhinal Cortex neurons in anaesthetized mice. We injected hyperpolarizing inputs representing inhibitory synaptic inputs along with sinusoidal oscillations and found that hyperpolarizing inputs injected at specific phases of oscillation had a higher probability of inducing subsequent spikes at the peak of the oscillation in some neurons. This effect was prominent in the cells with large sag potential, which is a marker of the h-current. In addition, larger and longer hyperpolarizing current square-pulse stimulation resulted in a larger probability of eliciting rebound spikes, though we did not observe a relationship between the amplitude or duration of hyperpolarizing current pulse stimulation and the delay of rebound spikes. Overall these results suggest that rebound spikes are observed in vivo and may play a role in generating grid cell activity in Medial Entorhinal Cortex neurons.
-
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, 2014Co-Authors: Michael E. HasselmoAbstract: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.
-
In vivo cholinergic modulation of the cellular properties of Medial Entorhinal Cortex neurons
The Journal of Physiology, 2013Co-Authors: Yusuke Tsuno, Nathan W. Schultheiss, Michael E. HasselmoAbstract:Key points • Medial Entorhinal Cortex neurons show special intrinsic properties in vitro, which might be important for contributing to functional cell properties, such as grid cell firing. • Both intrinsic properties in slices of Medial Entorhinal Cortex and grid cell activity in vivo are affected by cholinergic activation, but the relationships between these effects are unknown. • Using intracellular recording, we show that intrinsic properties including sag amplitude, sag time constant and resonance frequency are affected by cholinergic activation in vivo, and these results are consistent with in vitro studies. • Furthermore, we show that the relationship between firing frequency and input current is also changed by cholinergic activation in our in vivo recordings. • These results suggest the importance of cholinergic influences on the intrinsic properties of Medial Entorhinal neurons, and help us understand how this influence contributes to mechanisms of spatial memory and the cause of memory impairment. Abstract Extensive in vitro data and modeling studies suggest that intrinsic properties of Medial Entorhinal Cortex (MEC) neurons contribute to the spiking behaviour of functional cell types of MEC neurons, such as grid cells, recorded in behaving animals. It remains unclear, however, how intrinsic properties of MEC neurons influence cellular dynamics in intact networks in vivo. In order to begin to bridge the gap between electrophysiological data sets from brain slices and behaving animals, in the present study we performed intracellular recordings using sharp electrodes in urethane-anaesthetized rats to elucidate the cellular dynamics of MEC neurons in vivo. We focused on the h-current-dependent sag potential during hyperpolarizing current steps, subthreshold resonance in response to oscillatory frequency sweeps (chirp stimuli), persistent spiking in response to brief depolarizing inputs and the relationship between firing frequency and input (f–I curve), each of which is sensitive to cholinergic modulation in vitro. Consistent with data from in vitro studies, cholinergic activation by systemic application of the acetylcholinesterase inhibitor, physostigmine, resulted in decreased sag amplitude, increased sag time constant and a decrease of the peak resonance frequency. The f–I curve was also modulated by physostigmine in many neurons, but persistent spiking was not observed in any of our recordings, even when picrotoxin, a GABAA blocker, was included in the internal solution of the recording pipette to reduce possible effects of network inhibition. These results suggest that intrinsic oscillatory and rate-coding mechanisms, but not intrinsic bistability, are significantly modulated by acetylcholine in the intact Entorhinal network.
-
A computational intelligence approach to evaluation of membrane conductance interactions underlying persistent spiking, the f-I curve, and adaptive properties of Medial Entorhinal Cortex neurons
2012Co-Authors: T. Smolinski, Michael E. Hasselmo, P. Patel, Erik Fransén, Nathan W. SchultheissAbstract:A computational intelligence approach to evaluation of membrane conductance interactions underlying persistent spiking, the f-I curve, and adaptive properties of Medial Entorhinal Cortex neurons
Maybritt Moser - One of the best experts on this subject based on the ideXlab platform.
-
A Brainstem Locomotor Circuit Drives the Activity of Speed Cells in the Medial Entorhinal Cortex.
Cell Reports, 2020Co-Authors: Miguel M. Carvalho, Maybritt Moser, Emilio Kropff, Menno P. Witter, Nouk Tanke, Edvard I. MoserAbstract:Summary Locomotion activates an array of sensory inputs that may help build the self-position map of the Medial Entorhinal Cortex (MEC). In this map, speed-coding neurons are thought to dynamically update representations of the animal’s position. A possible origin for the Entorhinal speed signal is the mesencephalic locomotor region (MLR), which is critically involved in the activation of locomotor programs. Here, we describe, in rats, a circuit connecting the pedunculopontine tegmental nucleus (PPN) of the MLR to the MEC via the horizontal limb of the diagonal band of Broca (HDB). At each level of this pathway, locomotion speed is linearly encoded in neuronal firing rates. Optogenetic activation of PPN cells drives locomotion and modulates activity of speed-modulated neurons in HDB and MEC. Our results provide evidence for a pathway by which brainstem speed signals can reach cortical structures implicated in navigation and higher-order dynamic representations of space.
-
Object-vector coding in the Medial Entorhinal Cortex
Nature, 2019Co-Authors: Oyvind Arne Hoydal, Emilie Ranheim Skytoen, Maybritt Moser, Sebastian Ola Andersson, Edvard I. MoserAbstract:The hippocampus and the Medial Entorhinal Cortex are part of a brain system that maps self-location during navigation in the proximal environment1,2. In this system, correlations between neural firing and an animal’s position or orientation are so evident that cell types have been given simple descriptive names, such as place cells3, grid cells4, border cells5,6 and head-direction cells7. While the number of identified functional cell types is growing at a steady rate, insights remain limited by an almost-exclusive reliance on recordings from rodents foraging in empty enclosures that are different from the richly populated, geometrically irregular environments of the natural world. In environments that contain discrete objects, animals are known to store information about distance and direction to those objects and to use this vector information to guide navigation8–10. Theoretical studies have proposed that such vector operations are supported by neurons that use distance and direction from discrete objects11,12 or boundaries13,14 to determine the animal’s location, but—although some cells with vector-coding properties may be present in the hippocampus15 and subiculum16,17—it remains to be determined whether and how vectorial operations are implemented in the wider neural representation of space. Here we show that a large fraction of Medial Entorhinal Cortex neurons fire specifically when mice are at given distances and directions from spatially confined objects. These ‘object-vector cells’ are tuned equally to a spectrum of discrete objects, irrespective of their location in the test arena, as well as to a broad range of dimensions and shapes, from point-like objects to extended surfaces. Our findings point to vector coding as a predominant form of position coding in the Medial Entorhinal Cortex. Cells in the mouse Medial Entorhinal Cortex that fire when mice are at a specific distance and direction from a stationary object suggest that vector coding is important for rodent navigation.
-
functional properties of stellate cells in Medial Entorhinal Cortex layer ii
eLife, 2018Co-Authors: David C Rowland, Horstandreas Obenhaus, Emilie Ranheim Skytoen, Qiangwei Zhang, Clifford G Kentros, Edvard I. Moser, Maybritt MoserAbstract:: 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.
-
functional properties of stellate cells in Medial Entorhinal Cortex layer ii
eLife, 2018Co-Authors: David C Rowland, Horstandreas Obenhaus, Emilie Ranheim Skytoen, Qiangwei Zhang, Clifford G Kentros, Edvard I. Moser, Maybritt MoserAbstract:: 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.
-
Object-vector coding in the Medial Entorhinal Cortex
2018Co-Authors: Oyvind Arne Hoydal, Emilie Ranheim Skytoen, Maybritt Moser, Edvard I. MoserAbstract:Mammals use distances and directions from local objects to calculate trajectories during navigation but how such vectorial operations are implemented in neural representations of space has not been determined. Here we show in freely moving mice that a population of neurons in the Medial Entorhinal Cortex (MEC) responds specifically when the animal is at a given distance and direction from a spatially confined object. These "object-vector cells" are tuned similarly to a spectrum of discrete objects, irrespective of their location in the test arena. The vector relationships are expressed from the outset in novel environments with novel objects. Object-vector cells are distinct from grid cells, which use a distal reference frame, but the cells exhibit some mixed selectivity with head-direction and border cells. Collectively, these observations show that object locations are integrated in metric representations of self-location, with specific subsets of MEC neurons encoding vector relationships to individual objects.
Michael Brecht - One of the best experts on this subject based on the ideXlab platform.
-
Structural modularity and grid activity in the Medial Entorhinal Cortex
Journal of Neurophysiology, 2018Co-Authors: Robert K. Naumann, Michael Brecht, Patricia Preston-ferrer, Andrea BurgalossiAbstract: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...
-
Axonal synapse sorting in Medial Entorhinal Cortex
Nature, 2017Co-Authors: Helene Schmidt, Anjali Gour, Jakob Straehle, Kevin M. Boergens, Michael Brecht, Moritz HelmstaedterAbstract:Research on neuronal connectivity in the cerebral Cortex has focused on the existence and strength of synapses between neurons, and their location on the cell bodies and dendrites of postsynaptic neurons. The synaptic architecture of individual presynaptic axonal trees, however, remains largely unknown. Here we used dense reconstructions from three-dimensional electron microscopy in rats to study the synaptic organization of local presynaptic axons in layer 2 of the Medial Entorhinal Cortex, the site of grid-like spatial representations. We observe path-length-dependent axonal synapse sorting, such that axons of excitatory neurons sequentially target inhibitory neurons followed by excitatory neurons. Connectivity analysis revealed a cellular feedforward inhibition circuit involving wide, myelinated inhibitory axons and dendritic synapse clustering. Simulations show that this high-precision circuit can control the propagation of synchronized activity in the Medial Entorhinal Cortex, which is known for temporally precise discharges. Path-length-dependent axonal synapse sorting of local presynaptic axons of excitatory neurons in the rat Medial Entorhinal Cortex results in sequential targeting of inhibitory and excitatory neurons, which are connected by a cellular feedforward inhibition circuit. Specific neuronal connectivity is thought to be essential to computation by the cerebral Cortex, but electrophysiological measurements have provided only partial views of it. Moritz Helmstaedter and colleagues have produced a large-scale three-dimensional electron-microscopy dataset of the rat Medial Entorhinal Cortex, the grid-cells of which contribute to spatial navigation. This exhaustive connectomics mapping reveals a high degree of specificity in axonal projections, with interneurons being targeted before excitatory neurons, dendritic synapse clustering, and differential conduction velocities. These features should endow cortical circuits with exquisite spatial and temporal control in neuronal firing.
-
Complementary Modular Microcircuits of the Rat Medial Entorhinal Cortex
Frontiers in Systems Neuroscience, 2017Co-Authors: Saikat Ray, Michael Brecht, Andrea Burgalossi, Robert K. NaumannAbstract:The parahippocampal region is organized into different areas, with the Medial Entorhinal Cortex, presubiculum and parasubiculum prominent in spatial memory. Here we also describe a region at the extremity at of the Medial Entorhinal Cortex and bordering the subicular complex, the Medial-most part of the Entorhinal Cortex. While the subdivisions of hippocampus proper form more or less continuous cell sheets, the superficial layers of the parahippocampal region have a distinct modular architecture. We investigate the spatial distribution, laminar position, and putative connectivity of zinc-positive modules in layer 2 of the Medial Entorhinal Cortex of rats and relate them to the calbindin-positive patches previously described in the Entorhinal Cortex. We found that the zinc-positive modules are complementary to the previously described calbindin-positive patches. We also found that inputs from the presubiculum are directed towards the zinc-positive modules while the calbindin-positive patches received inputs from the parasubiculum. Notably, the dendrites of neurons from layers 3 and 5, positive for Purkinje Cell Protein 4 expression, overlap with the zinc modules. Our data thus indicate that these two complementary modular systems, the calbindin patches and zinc modules, are part of parallel information streams in the hippocampal formation.
-
Structural development and dorsoventral maturation of the Medial Entorhinal Cortex
eLife, 2016Co-Authors: Saikat Ray, Michael BrechtAbstract:We investigated the structural development of superficial-layers of Medial Entorhinal Cortex and parasubiculum in rats. The grid-layout and cholinergic-innervation of calbindin-positive pyramidal-cells in layer-2 emerged around birth while reelin-positive stellate-cells were scattered throughout development. Layer-3 and parasubiculum neurons had a transient calbindin-expression, which declined with age. Early postnatally, layer-2 pyramidal but not stellate-cells co-localized with doublecortin - a marker of immature neurons - suggesting delayed functional-maturation of pyramidal-cells. Three observations indicated a dorsal-to-ventral maturation of Entorhinal Cortex and parasubiculum: (i) calbindin-expression in layer-3 neurons decreased progressively from dorsal-to-ventral, (ii) doublecortin in layer-2 calbindin-positive-patches disappeared dorsally before ventrally, and (iii) wolframin-expression emerged earlier in dorsal than ventral parasubiculum. The early appearance of calbindin-pyramidal-grid-organization in layer-2 suggests that this pattern is instructed by genetic information rather than experience. Superficial-layer-microcircuits mature earlier in dorsal Entorhinal Cortex, where small spatial-scales are represented. Maturation of ventral-Entorhinal-microcircuits - representing larger spatial-scales - follows later around the onset of exploratory behavior.
-
Grid-Layout and Theta-Modulation of Layer 2 Pyramidal Neurons in Medial Entorhinal Cortex
Science, 2014Co-Authors: Saikat Ray, Helene Schmidt, Andrea Burgalossi, Robert K. Naumann, Qiusong Tang, Michael BrechtAbstract:Little is known about how microcircuits are organized in layer 2 of the Medial Entorhinal Cortex. We visualized principal cell microcircuits and determined cellular theta-rhythmicity in freely moving rats. Non–dentate-projecting, calbindin-positive pyramidal cells bundled dendrites together and formed patches arranged in a hexagonal grid aligned to layer 1 axons, parasubiculum, and cholinergic inputs. Calbindin-negative, dentate-gyrus–projecting stellate cells were distributed across layer 2 but avoided centers of calbindin-positive patches. Cholinergic drive sustained theta-rhythmicity, which was twofold stronger in pyramidal than in stellate neurons. Theta-rhythmicity was cell-type–specific but not distributed as expected from cell-intrinsic properties. Layer 2 divides into a weakly theta-locked stellate cell lattice and spatiotemporally highly organized pyramidal grid. It needs to be assessed how these two distinct principal cell networks contribute to grid cell activity.