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Journal ArticleDOI

Recurrent inhibitory circuitry as a mechanism for grid formation

TL;DR: It is demonstrated that stellate cells, the principal cell type in the layer II grid network, are mainly interconnected via inhibitory interneurons, and that stable grid firing can emerge from a simple recurrent inhibitory network.
Abstract: Grid cells in layer II of the medial entorhinal cortex form a principal component of the mammalian neural representation of space. The firing pattern of a single grid cell has been hypothesized to be generated through attractor dynamics in a network with a specific local connectivity including both excitatory and inhibitory connections. However, experimental evidence supporting the presence of such connectivity among grid cells in layer II is limited. Here we report recordings from more than 600 neuron pairs in rat entorhinal slices, demonstrating that stellate cells, the principal cell type in the layer II grid network, are mainly interconnected via inhibitory interneurons. Using a model attractor network, we demonstrate that stable grid firing can emerge from a simple recurrent inhibitory network. Our findings thus suggest that the observed inhibitory microcircuitry between stellate cells is sufficient to generate grid-cell firing patterns in layer II of the medial entorhinal cortex.
Citations
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Journal ArticleDOI
20 Jul 2016-Neuron
TL;DR: Current understanding of neocortical interneuron diversity and the properties that distinguish cell types are reviewed and it is illustrated how recent advances in the field have shed light onto the mechanisms by which GABAergic inhibition contributes to network operations.

1,358 citations


Cites background from "Recurrent inhibitory circuitry as a..."

  • ...…forms that FBI encompasses have been proposed to participate in important phenomena such as surround suppression (Adesnik et al., 2012), assembly selection and competition (Roux and Buzsáki, 2015), oscillatory coupling (Buzsáki and Wang, 2012), and grid field formation (Couey et al., 2013)....

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Journal ArticleDOI
TL;DR: It is shown that removal of perineuronal nets leads to lower inhibitory spiking activity, and reduces grid cells’ ability to create stable representations of a novel environment, and that PNN removal in entorhinal cortex distorted spatial representations in downstream hippocampal neurons.
Abstract: Grid cells are part of a widespread network which supports navigation and spatial memory. Stable grid patterns appear late in development, in concert with extracellular matrix aggregates termed perineuronal nets (PNNs) that condense around inhibitory neurons. It has been suggested that PNNs stabilize synaptic connections and long-term memories, but their role in the grid cell network remains elusive. We show that removal of PNNs leads to lower inhibitory spiking activity, and reduces grid cells' ability to create stable representations of a novel environment. Furthermore, in animals with disrupted PNNs, exposure to a novel arena corrupted the spatiotemporal relationships within grid cell modules, and the stored representations of a familiar arena. Finally, we show that PNN removal in entorhinal cortex distorted spatial representations in downstream hippocampal neurons. Together this work suggests that PNNs provide a key stabilizing element for the grid cell network.

935 citations

Journal ArticleDOI
01 Aug 2014-Science
TL;DR: Not only are PV+ interneurons involved in basic microcircuit functions, but they also play a role in complex network operations, including expansion of dynamic activity range, pattern separation, modulation of place and grid field shapes, phase precession, and gain modulation of sensory responses.
Abstract: The success story of fast-spiking, parvalbumin-positive (PV(+)) GABAergic interneurons (GABA, γ-aminobutyric acid) in the mammalian central nervous system is noteworthy. In 1995, the properties of these interneurons were completely unknown. Twenty years later, thanks to the massive use of subcellular patch-clamp techniques, simultaneous multiple-cell recording, optogenetics, in vivo measurements, and computational approaches, our knowledge about PV(+) interneurons became more extensive than for several types of pyramidal neurons. These findings have implications beyond the "small world" of basic research on GABAergic cells. For example, the results provide a first proof of principle that neuroscientists might be able to close the gaps between the molecular, cellular, network, and behavioral levels, representing one of the main challenges at the present time. Furthermore, the results may form the basis for PV(+) interneurons as therapeutic targets for brain disease in the future. However, much needs to be learned about the basic function of these interneurons before clinical neuroscientists will be able to use PV(+) interneurons for therapeutic purposes.

899 citations


Cites background from "Recurrent inhibitory circuitry as a..."

  • ...Reciprocal coupling between principal neurons and fast-spiking interneurons has been demonstrated in several circuits, including the hippocampus and the entorhinal cortex (23, 75) (Fig....

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  • ...Under certain conditions, network models with recurrent inhibitory connectivity are also able to generate grid cell response patterns (75, 81) (Fig....

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  • ...Quadruple recording in the entorhinal cortex also suggests a substantial contribution of PV interneurons to both recurrent and lateral inhibition (75)....

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Journal ArticleDOI
23 Jul 2015-Nature
TL;DR: It is shown that running speed is represented in the firing rate of a ubiquitous but functionally dedicated population of entorhinal neurons distinct from other cell populations of the local circuit, such as grid, head-direction and border cells.
Abstract: Grid cells in the medial entorhinal cortex have spatial firing fields that repeat periodically in a hexagonal pattern When animals move, activity is translated between grid cells in accordance with the animal's displacement in the environment For this translation to occur, grid cells must have continuous access to information about instantaneous running speed However, a powerful entorhinal speed signal has not been identified Here we show that running speed is represented in the firing rate of a ubiquitous but functionally dedicated population of entorhinal neurons distinct from other cell populations of the local circuit, such as grid, head-direction and border cells These 'speed cells' are characterized by a context-invariant positive, linear response to running speed, and share with grid cells a prospective bias of ∼50-80 ms Our observations point to speed cells as a key component of the dynamic representation of self-location in the medial entorhinal cortex

560 citations

Journal ArticleDOI
TL;DR: It is now possible to investigate how specialized cell types of hippocampal–entorhinal systems work together, and spatial mapping may become one of the first cognitive functions to be understood in mechanistic detail.
Abstract: Since the first place cell was recorded and the cognitive-map theory was subsequently formulated, investigation of spatial representation in the hippocampal formation has evolved in stages. Early studies sought to verify the spatial nature of place cell activity and determine its sensory origin. A new epoch started with the discovery of head direction cells and the realization of the importance of angular and linear movement-integration in generating spatial maps. A third epoch began when investigators turned their attention to the entorhinal cortex, which led to the discovery of grid cells and border cells. This review will show how ideas about integration of self-motion cues have shaped our understanding of spatial representation in hippocampal-entorhinal systems from the 1970s until today. It is now possible to investigate how specialized cell types of these systems work together, and spatial mapping may become one of the first cognitive functions to be understood in mechanistic detail.

344 citations

References
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Book
01 Jan 1983
TL;DR: This paper presents a meta-analyses of the determinants of earthquake-triggered landsliding in the Czech Republic over a period of 18 months in order to establish a probabilistic framework for estimating the intensity of the earthquake.
Abstract: Preface. Acknowledgements. Introduction. References. List of Structures. Index of Abbreviations. Diagrams.

57,116 citations

Journal ArticleDOI
TL;DR: The latest red version matures more completely, is more tolerant of N-terminal fusions and is over tenfold more photostable than mRFP1, and three monomers with distinguishable hues from yellow-orange to red-orange have higher quantum efficiencies.
Abstract: Fluorescent proteins are genetically encoded, easily imaged reporters crucial in biology and biotechnology. When a protein is tagged by fusion to a fluorescent protein, interactions between fluorescent proteins can undesirably disturb targeting or function. Unfortunately, all wild-type yellow-to-red fluorescent proteins reported so far are obligately tetrameric and often toxic or disruptive. The first true monomer was mRFP1, derived from the Discosoma sp. fluorescent protein "DsRed" by directed evolution first to increase the speed of maturation, then to break each subunit interface while restoring fluorescence, which cumulatively required 33 substitutions. Although mRFP1 has already proven widely useful, several properties could bear improvement and more colors would be welcome. We report the next generation of monomers. The latest red version matures more completely, is more tolerant of N-terminal fusions and is over tenfold more photostable than mRFP1. Three monomers with distinguishable hues from yellow-orange to red-orange have higher quantum efficiencies.

4,607 citations

Journal ArticleDOI
TL;DR: In this paper, the authors adapted the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons.
Abstract: Temporally precise, noninvasive control of activity in well-defined neuronal populations is a long-sought goal of systems neuroscience. We adapted for this purpose the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons. We demonstrate reliable, millisecond-timescale control of neuronal spiking, as well as control of excitatory and inhibitory synaptic transmission. This technology allows the use of light to alter neural processing at the level of single spikes and synaptic events, yielding a widely applicable tool for neuroscientists and biomedical engineers.

4,411 citations

Journal ArticleDOI
11 Aug 2005-Nature
TL;DR: The dorsocaudal medial entorhinal cortex (dMEC) contains a directionally oriented, topographically organized neural map of the spatial environment, whose key unit is the ‘grid cell’, which is activated whenever the animal's position coincides with any vertex of a regular grid of equilateral triangles spanning the surface of the environment.
Abstract: The ability to find one's way depends on neural algorithms that integrate information about place, distance and direction, but the implementation of these operations in cortical microcircuits is poorly understood. Here we show that the dorsocaudal medial entorhinal cortex (dMEC) contains a directionally oriented, topographically organized neural map of the spatial environment. Its key unit is the 'grid cell', which is activated whenever the animal's position coincides with any vertex of a regular grid of equilateral triangles spanning the surface of the environment. Grids of neighbouring cells share a common orientation and spacing, but their vertex locations (their phases) differ. The spacing and size of individual fields increase from dorsal to ventral dMEC. The map is anchored to external landmarks, but persists in their absence, suggesting that grid cells may be part of a generalized, path-integration-based map of the spatial environment.

3,445 citations


"Recurrent inhibitory circuitry as a..." refers background or methods in this paper

  • ...that includes a reciprocally connected cell pair consisting of one fast-spiking interneuron (1)...

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  • ...The simulation then consisted of integrating equation (1) with a 1-ms time step over a contiguous 10-min path taken from the experiments with varying parameters of the connectivity W0 and R as shown in Figure 3....

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Journal ArticleDOI
TL;DR: The dynamics of pattern formation is studied for lateral-inhibition type homogeneous neural fields with general connections and it is proved that there are five types of pattern dynamics.
Abstract: The dynamics of pattern formation is studied for lateral-inhibition type homogeneous neural fields with general connections. Neural fields consisting of single layer are first treated, and it is proved that there are five types of pattern dynamics. The type of the dynamics of a field depends not only on the mutual connections within the field but on the level of homogeneous stimulus given to the field. An example of the dynamics is as follows: A fixed size of localized excitation, once evoked by stimulation, can be retained in the field persistently even after the stimulation vanishes. It moves until it finds the position of the maximum of the input stimulus. Fields consisting of an excitatory and an inhibitory layer are next analyzed. In addition to stationary localized excitation, fields have such pattern dynamics as production of oscillatory waves, travelling waves, active and dual active transients, etc.

1,996 citations