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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 demonstrated that nicotine modulates γ oscillations via α7 and α4β2 nAChR as well as NMDA activation, suggesting that nA ChR activation may have a therapeutic role for the clinical disorder such as schizophrenia, which is known to have impaired γscillation and hypo-NMDA receptor function.
Abstract: γ oscillations are associated with higher brain functions such as memory, perception and consciousness. Disruption of γ oscillations occur in various neuro-psychological disorders such as schizophrenia. Nicotinic acetylcholine receptors (nAChR) are highly expressed in the hippocampus, however, little is known about the role on hippocampal persistent γ oscillation. This study examined the effects of nicotine and selective nAChR agonists and antagonists on kainate-induced persistent γ oscillation in rat hippocampal slices. Nicotine enhanced γ oscillation at concentrations of 0.1–10 μM, but reduced it at a higher concentration of 100 μM. The enhancement on γ oscillation can be best mimicked by co-application of α4β2- and α7- nAChR agonist and reduced by a combination of nAChR antagonists, DhβE and MLA. However, these nAChR antagonists failed to block the suppressing role of nicotine on γ. Furthermore, we found that the NMDA receptor antagonist D-AP5 completely blocked the effect of nicotine. These results demonstrate that nicotine modulates γ oscillations via α7 and α4β2 nAChR as well as NMDA activation, suggesting that nAChR activation may have a therapeutic role for the clinical disorder such as schizophrenia, which is known to have impaired γ oscillation and hypo-NMDA receptor function.

27 citations

Journal ArticleDOI
TL;DR: Aβ overexpression in a second-generation Alzheimer's disease model results in alterations in anxiety-type behaviours, as well as gamma oscillations, neural organisation and Grin2b expression in the prefrontal cortex.
Abstract: We studied a new amyloid-beta precursor protein (App) knock-in mouse model of Alzheimer's disease (AppNL-G-F ), containing the Swedish KM670/671NL mutation, the Iberian I716F mutation and the Artic E693G mutation, which generates elevated levels of amyloid beta (Aβ)40 and Aβ42 without the confounds associated with APP overexpression. This enabled us to assess changes in anxiety-related and social behaviours, and neural alterations potentially underlying such changes, driven specifically by Aβ accumulation. AppNL-G-F knock-in mice exhibited subtle deficits in tasks assessing social olfaction, but not in social motivation tasks. In anxiety-assessing tasks, AppNL-G-F knock-in mice exhibited: (1) increased thigmotaxis in the open field (OF), yet; (2) reduced closed-arm, and increased open-arm, time in the elevated plus maze (EPM). Their ostensibly anxiogenic OF profile, yet ostensibly anxiolytic EPM profile, could hint at altered cortical mechanisms affecting decision-making (e.g. 'disinhibition'), rather than simple core deficits in emotional motivation. Consistent with this possibility, alterations in microstructure, glutamatergic-dependent gamma oscillations and glutamatergic gene expression were all observed in the prefrontal cortex, but not the amygdala, of AppNL-G-F knock-in mice. Thus, insoluble Aβ overexpression drives prefrontal cortical alterations, potentially underlying changes in social and anxiety-related behavioural tasks.This article has an associated First Person interview with the first author of the paper.

27 citations


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

  • ...Furthermore, NMDA receptors are necessary for gamma oscillations mediated by the goblet cell interneurons within the entorhinal cortex (Middleton et al., 2008), with specific antagonism of GluN2B significantly reducing hippocampal gamma power (Hanson et al....

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  • ...Furthermore, NMDA receptors are necessary for gamma oscillations mediated by the goblet cell interneurons within the entorhinal cortex (Middleton et al., 2008), with specific antagonism of GluN2B significantly reducing hippocampal gamma power (Hanson et al., 2013)....

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  • ..., 2011), by modifying recruitment of different interneuron subpopulations (Middleton et al., 2008)....

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  • ...…using kainate and tested their dependency on NMDA receptors, which have previously been shown to modulate peak frequency through inhibitory postsynaptic currents (Carlén et al., 2012; McNally et al., 2011), by modifying recruitment of different interneuron subpopulations (Middleton et al., 2008)....

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Journal ArticleDOI
TL;DR: It is proposed that the psychedelic effects of ketamine may involve the inhibition of STP and, potentially, associated forms of working memory, which is a novel candidate mechanism for some effects ofketamine.

26 citations

Journal ArticleDOI
TL;DR: A computational model of competitive selection between multiple stimuli, where the selection and transfer of population-encoded information arises from competition between converging stimuli to entrain a target population of neurons, is developed.
Abstract: The role of gamma frequency oscillation in neuronal interaction, and the relationship between oscillation and information transfer between neurons, has been the focus of much recent research. While the biological mechanisms responsible for gamma oscillation and the properties of resulting networks are well studied, the dynamics of changing phase relationships and mechanisms underlying the formation of phase coherence between oscillating neuronal populations are not well understood. To this end we develop a computational model of competitive selection between multiple stimuli, where selection and the transfer of population-encoded information arises from competition between converging stimuli to entrain a target population of neurons. Oscillation is generated by Pyramidal-Interneuronal Network Gamma through the action of recurrent synaptic connections between a locally connected network of excitatory and inhibitory neurons. Competition between stimuli is driven by differences in coherence of oscillation, while transmission of a single selected stimulus is enabled between generating and receiving neurons via Communication-through-Coherence. We explore the effect of varying synaptic parameters on the competitive transmission of stimuli over different neuron models, and identify a continuous region within the parameter space of the recurrent synaptic loop where inhibition-induced oscillation results in entrainment of target neurons. Within this optimal region we find that competition between stimuli of equal coherence results in model output that alternates between representation of the stimuli, in a manner strongly resembling well-known biological phenomena resulting from competitive stimulus selection such as binocular rivalry.

26 citations


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

  • ...…Sejnowski, 2009; Wang, 2010), long-range synchronization (Roelfsema et al., 1997; Uhlhaas et al., 2009), and the role of different classes of inhibitory interneurons in generating and maintaining oscillation (Whittington and Traub, 2003; Middleton et al., 2008) have been extensively investigated....

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Journal ArticleDOI
TL;DR: The data show the BLA capable of generating gamma rhythms in common with other cortical areas studied to date, the network mechanisms appear to be different, suggesting a unique network structure underlies amygdala rhythmogenesis.
Abstract: The basolateral amygdala (BLA) has a fundamental role in affective processing. In vivo studies have revealed rhythmic population activity of a similar type to that seen in the hippocampus and cortical areas during learning tasks. The amygdala contains densely interconnected networks of inhibitory interneurons similar to those responsible for fast network activity generation in the hippocampus and other cortical structures. Here we report that neuronal networks of the BLA in isolation generate persistent, gamma frequency (30–80 Hz) oscillations upon kainate receptor activation with kainic acid. We show that, like other cortical structures, BLA oscillations are completely dependent upon γ-aminobutyric acid (GABA)ergic inhibition. GABAA receptor blockade abolished all oscillations, and the activity was also sensitive to the barbiturate, pentobarbital. Blockade of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors or N-methyl-d-aspartate (NMDA) receptors had no significant effect on gamma activity. However, the GluR5-containing kainate receptor-specific antagonist (S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxybenzyl) pyrimidine-2,4-dione (UBP302) abolished oscillations–evidence that glutamatergic receptor involvement is predominantly kainate receptor mediated. The mixed AMPA/kainate receptor antagonist 6-nitro-7-sulphamoylbenzo[f]quinoxalone-2,3-dione disodium (NBQX) abolished all oscillatory activity in 8/14 of slices tested. In the remaining slices, gamma frequency activity was abolished to reveal a low-amplitude, NMDA receptor-dependent, beta frequency (10–20 Hz) oscillation. Gamma oscillations are abolished by gap junction blockade. While these data show the BLA capable of generating gamma rhythms in common with other cortical areas studied to date, the network mechanisms appear to be different, suggesting a unique network structure underlies amygdala rhythmogenesis. Understanding how BLA networks produce synchronous activity is paramount to understanding how the BLA executes influence on important cognitive processes such as emotional learning.

26 citations


Additional excerpts

  • ...The gamma rhythm generated was near-identical to that seen for gamma rhythms in area CA3 (30–40 Hz), but slower than that reported for area CA1 in the hippocampus (40–100 Hz; Middleton et al., 2008a,b)....

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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)....

    [...]

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