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Journal ArticleDOI

NMDA receptor-dependent switching between different gamma rhythm-generating microcircuits in entorhinal cortex

TL;DR: The two different gamma frequencies matched the different intrinsic frequencies in hippocampal areas CA3 and CA1, suggesting that NMDA receptor activation may control the nature of temporal interactions between mEC and hippocampus, thus influencing the pathway for information transfer between the two regions.
Abstract: Local circuits in the medial entorhinal cortex (mEC) and hippocampus generate gamma frequency population rhythms independently. Temporal interaction between these areas at gamma frequencies is implicated in memory—a phenomenon linked to activity of NMDA-subtype glutamate receptors. While blockade of NMDA receptors does not affect frequency of gamma rhythms in hippocampus, it exposes a second, lower frequency (25–35 Hz) gamma rhythm in mEC. In experiment and model, NMDA receptor-dependent mEC gamma rhythms were mediated by basket interneurons, but NMDA receptor-independent gamma rhythms were mediated by a novel interneuron subtype—the goblet cell. This cell was distinct from basket cells in morphology, intrinsic membrane properties and synaptic inputs. The two different gamma frequencies matched the different intrinsic frequencies in hippocampal areas CA3 and CA1, suggesting that NMDA receptor activation may control the nature of temporal interactions between mEC and hippocampus, thus influencing the pathway for information transfer between the two regions.

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Citations
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Journal ArticleDOI
TL;DR: It is proposed that analogous signal-to-noise deficits in the flow of cortical information in preclinical models are useful targets for the development of new drugs that target the treatment-resistant symptoms of schizophrenia.

263 citations


Cites background from "NMDA receptor-dependent switching b..."

  • ...There have been some reports that NMDA-receptors on PV interneurons are more sensitive to pharmacologic blockade than receptors expressed on excitatory pyramidal cells, particularly in the hippocampus and entorhinal cortex (Grunze et al., 1996; Jones and Buhl, 1993; Middleton et al., 2008)....

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Journal ArticleDOI
TL;DR: It is concluded that most massively parallel brain regions have different mechanisms of gamma rhythm generation, that different mechanisms have distinct functional correlates, and that switching between different local modes of gamma generation may be an effective way to direct cortical communication streams.
Abstract: Gamma rhythms (30–80 Hz) are a near-ubiquitous feature of neuronal population activity in mammalian cortices. Their dynamic properties permit the synchronization of neuronal responses to sensory input within spatially distributed networks, transient formation of local neuronal “cell assemblies,” and coherent response patterns essential for intercortical regional communication. Each of these phenomena form part of a working hypothesis for cognitive function in cortex. All forms of physiological gamma rhythm are inhibition based, being characterized by rhythmic trains of inhibitory postsynaptic potentials in populations of principal neurons. It is these repeating periods of relative enhancement and attenuation of the responsivity of major cell groups in cortex that provides a temporal structure shared across many millions of neurons. However, when considering the origins of these repeating trains of inhibitory events considerable divergence is seen depending on cortical region studied and mode of activation of gamma rhythm generating networks. Here, we review the evidence for involvement of multiple subtypes of interneuron and focus on different modes of activation of these cells. We conclude that most massively parallel brain regions have different mechanisms of gamma rhythm generation, that different mechanisms have distinct functional correlates, and that switching between different local modes of gamma generation may be an effective way to direct cortical communication streams. Finally, we suggest that developmental disruption of the endophenotype for certain subsets of gamma-generating interneuron may underlie cognitive deficit in psychiatric illness. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 92–106, 2011

249 citations


Cites background from "NMDA receptor-dependent switching b..."

  • ...…depolarization of interneurons in entorhinal cortex may serve to dynamically route inputs to the hippocampus, with CA3 networks being tuned to the goblet cell-mediated slower gamma rhythm and CA1 networks being tuned to the basket cell (higher frequency) gamma rhythm (Middleton et al., 2008a, b)....

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  • ...Here, cholinergic activation via nicotinic receptors generates a gamma frequency local field potential oscillation that is independent of any kainate, AMPA or NMDA receptor activity [Fig 2(A); (Middleton et al., 2008a, b)]....

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  • ...Further evidence from medial entorhinal cortex has shown that two anatomically distinct subclasses of local circuit interneuron in superficial layers compete for control over gamma rhythm generation (Middleton et al., 2008a, b; Fig....

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Journal ArticleDOI
TL;DR: It is found that the frequency of in vitro cholinergically induced gamma oscillations in the mouse hippocampal CA3 region was increased by the activation of NMDA receptors (NMDARs) on interneurons, and the NMDAR-dependent increase of gamma oscillation frequency was counteracted by the tonic inhibition of the interneuron mediated by δ subunit–containing GABAARs.
Abstract: Gamma-frequency oscillations depend on phasic synaptic GABA(A) receptor (GABA(A)R)-mediated inhibition to synchronize spike timing. The spillover of synaptically released GABA can also activate extrasynaptic GABA(A)Rs, and such tonic inhibition may also contribute to modulating network dynamics. In many neuronal cell types, tonic inhibition is mediated by delta subunit-containing GABA(A)Rs. We found that the frequency of in vitro cholinergically induced gamma oscillations in the mouse hippocampal CA3 region was increased by the activation of NMDA receptors (NMDARs) on interneurons. The NMDAR-dependent increase of gamma oscillation frequency was counteracted by the tonic inhibition of the interneurons mediated by delta subunit-containing GABA(A)Rs. Recordings of synaptic currents during gamma activity revealed that NMDAR-mediated increases in oscillation frequency correlated with a progressive synchronization of phasic excitation and inhibition in the network. Thus, the balance between tonic excitation and tonic inhibition of interneurons may modulate gamma frequency by shaping interneuronal synchronization.

222 citations

Journal ArticleDOI
TL;DR: The contributions of rhythms to basic cognitive computations and to major cognitive functions (such as attention and multi‐modal coordination) are investigated and the premise that the physiology underlying brain rhythms plays an essential role in how these rhythms facilitate some cognitive operations is offered.
Abstract: Neuronal rhythms are ubiquitous features of brain dynamics, and are highly correlated with cognitive processing. However, the relationship between the physiological mechanisms producing these rhythms and the functions associated with the rhythms remains mysterious. This article investigates the contributions of rhythms to basic cognitive computations (such as filtering signals by coherence and/or frequency) and to major cognitive functions (such as attention and multi-modal coordination). We offer support to the premise that the physiology underlying brain rhythms plays an essential role in how these rhythms facilitate some cognitive operations.

197 citations


Cites background from "NMDA receptor-dependent switching b..."

  • ...An example of the importance of such frequency matching is given by a striking observation (Middleton et al., 2008) that the rodent entorhinal cortex, in vitro, can produce two different frequencies of gamma rhythm, separated by ~10 Hz, depending on the activity of N-methyl-D-aspartate (NMDA)…...

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Journal ArticleDOI
TL;DR: It is found that EC5 and EC2 principal neurons form large axonal networks mainly within their layers, interconnected by the more vertically organized axon trees of EC3 pyramidal cells, which may underlie their behaviorally distinct firing patterns in the waking animal.
Abstract: A thorough knowledge of the intrinsic circuit properties of the entorhinal cortex (EC) and the temporal dynamics these circuits support is essential for understanding how information is exchanged between the hippocampus and neocortex. Using intracellular and extracellular recordings in the anesthetized rat and anatomical reconstruction of single cells, we found that EC5 and EC2 principal neurons form large axonal networks mainly within their layers, interconnected by the more vertically organized axon trees of EC3 pyramidal cells. Principal cells showed layer-specific unique membrane properties and contributed differentially to theta and gamma oscillations. EC2 principal cells were most strongly phase modulated by EC theta. The multiple gamma oscillators, present in the various EC layers, were temporally coordinated by the phase of theta waves. Putative interneurons in all EC layers fired relatively synchronously within the theta cycle, coinciding with the maximum power of gamma oscillation. The special wiring architecture and unique membrane properties of EC neurons may underlie their behaviorally distinct firing patterns in the waking animal.

194 citations


Cites background from "NMDA receptor-dependent switching b..."

  • ...The spatial and temporal segregation of EC gamma rhythms may engage different regions of the hippocampus in a task-specific manner (Charpak et al., 1995; Chrobak and Buzsáki, 1998; Middleton et al., 2008; Colgin et al., 2009)....

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  • ...Gamma oscillations in the EC may arise from multiple mechanisms (Cunningham et al., 2003, 2004, 2006; Middleton et al., 2008)....

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  • ...In agreement with in vitro studies (Cunningham et al., 2003; Middleton et al., 2008), we found that gamma oscillations independently emerged in different layers....

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References
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Journal ArticleDOI
15 Sep 2006-Science
TL;DR: The results indicate that transient coupling between low- and high-frequency brain rhythms coordinates activity in distributed cortical areas, providing a mechanism for effective communication during cognitive processing in humans.
Abstract: We observed robust coupling between the high- and low-frequency bands of ongoing electrical activity in the human brain. In particular, the phase of the low-frequency theta (4 to 8 hertz) rhythm modulates power in the high gamma (80 to 150 hertz) band of the electrocorticogram, with stronger modulation occurring at higher theta amplitudes. Furthermore, different behavioral tasks evoke distinct patterns of theta/high gamma coupling across the cortex. The results indicate that transient coupling between low- and high-frequency brain rhythms coordinates activity in distributed cortical areas, providing a mechanism for effective communication during cognitive processing in humans.

2,404 citations


"NMDA receptor-dependent switching b..." refers background in this paper

  • ...This mechanism can underlie gamma rhythms in a broad range of frequencies from around 20 Hz up to 70 Hz in the hippocampus (8) but cannot support higher frequencies such as those labeled as ‘‘high gamma’’ previously (9)....

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Journal ArticleDOI
16 Feb 1995-Nature
TL;DR: It is proposed that interneuron network oscillations, in conjunction with intrinsic membrane resonances and long-loop (such as thalamocortical) interactions, contribute to 40-Hz rhythms in vivo.
Abstract: Partially synchronous 40-Hz oscillations of cortical neurons have been implicated in cognitive function. Specifically, coherence of these oscillations between different parts of the cortex may provide conjunctive properties to solve the 'binding problem': associating features detected by the cortex into unified perceived objects. Here we report an emergent 40-Hz oscillation in networks of inhibitory neurons connected by synapses using GABAA (gamma-aminobutyric acid) receptors in slices of rat hippocampus and neocortex. These network inhibitory postsynaptic potential oscillations occur in response to the activation of metabotropic glutamate receptors. The oscillations can entrain pyramidal cell discharges. The oscillation frequency is determined both by the net excitation of interneurons and by the kinetics of the inhibitory postsynaptic potentials between them. We propose that interneuron network oscillations, in conjunction with intrinsic membrane resonances and long-loop (such as thalamocortical) interactions, contribute to 40-Hz rhythms in vivo.

1,625 citations


"NMDA receptor-dependent switching b..." refers background in this paper

  • ...The basic mechanism of generation of population gamma rhythms by local neuronal circuits reveals an absolute dependence on the influence of fast spiking inhibitory interneurons at the level of principal cell somata (5, 6),with the frequency dependent on the magnitude and kinetics of gamma aminobutyric acid (GABAA) receptor-mediated synaptic events (7)....

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Journal ArticleDOI
Anatol Bragin1, G. Jandó1, Zoltan Nadasdy1, J Hetke1, K Wise1, György Buzsáki1 
TL;DR: It is suggested that gamma oscillation emerges from an interaction between intrinsic oscillatory properties of interneurons and the network properties of the dentate gyrus and that Gamma oscillation in the CA3-CA1 circuitry is suppressed by either the hilar region or the entorhinal cortex.
Abstract: The cellular generation and spatial distribution of gamma frequency (40-100 Hz) activity was examined in the hippocampus of the awake rat. Field potentials and unit activity were recorded by multiple site silicon probes (5- and 16-site shanks) and wire electrode arrays. Gamma waves were highly coherent along the long axis of the dentate hilus, but average coherence decreased rapidly in the CA3 and CA1 directions. Analysis of short epochs revealed large fluctuations in coherence values between the dentate and CA1 gamma waves. Current source density analysis revealed large sinks and sources in the dentate gyrus with spatial distribution similar to the dipoles evoked by stimulation of the perforant path. The frequency changes of gamma and theta waves positively correlated (40-100 Hz and 5-10 Hz, respectively). Putative interneurons in the dentate gyrus discharged at gamma frequency and were phase-locked to the ascending part of the gamma waves recorded from the hilus. Following bilateral lesion of the entorhinal cortex the power and frequency of hilar gamma activity significantly decreased or disappeared. Instead, a large amplitude but slower gamma pattern (25-50 Hz) emerged in the CA3-CA1 network. We suggest that gamma oscillation emerges from an interaction between intrinsic oscillatory properties of interneurons and the network properties of the dentate gyrus. We also hypothesize that under physiological conditions the hilar gamma oscillation may be entrained by the entorhinal rhythm and that gamma oscillation in the CA3-CA1 circuitry is suppressed by either the hilar region or the entorhinal cortex.

1,529 citations


"NMDA receptor-dependent switching b..." refers background in this paper

  • ...For example, removal of entorhinal cortex in vivo produces a slower gamma rhythm (39), whose origins appear to be in area CA3 (40)....

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Journal ArticleDOI
23 Jan 2003-Neuron
TL;DR: This work examines the generation of gamma oscillation currents in the hippocampus, using two-dimensional, 96-site silicon probes and identifies two gamma generators, one in the dentate gyrus and another in the CA3-CA1 regions.

985 citations


"NMDA receptor-dependent switching b..." refers background in this paper

  • ...For example, removal of entorhinal cortex in vivo produces a slower gamma rhythm (39), whose origins appear to be in area CA3 (40)....

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Journal ArticleDOI
21 Mar 2008-Science
TL;DR: In this paper, the authors used high-resolution (1.5-millimeter isotropic voxels) functional magnetic resonance imaging to measure brain activity during incidental memory encoding.
Abstract: Pattern separation, the process of transforming similar representations or memories into highly dissimilar, nonoverlapping representations, is a key component of many functions ascribed to the hippocampus. Computational models have stressed the role of the hippocampus and, in particular, the dentate gyrus and its projections into the CA3 subregion in pattern separation. We used high-resolution (1.5-millimeter isotropic voxels) functional magnetic resonance imaging to measure brain activity during incidental memory encoding. Although activity consistent with a bias toward pattern completion was observed in CA1, the subiculum, and the entorhinal and parahippocampal cortices, activity consistent with a strong bias toward pattern separation was observed in, and limited to, the CA3/dentate gyrus. These results provide compelling evidence of a key role of the human CA3/dentate gyrus in pattern separation.

899 citations