NMDA receptor-dependent switching between different gamma rhythm-generating microcircuits in entorhinal cortex
25 Nov 2008-Proceedings of the National Academy of Sciences of the United States of America (National Academy of Sciences)-Vol. 105, Iss: 47, pp 18572-18577
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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TL;DR: In the medial entorhinal cortex (MEC), a large proportion of neurons encoding aspects of the organism's spatial surroundings are encoded by local micro-circuits as discussed by the authors .
Abstract: The hippocampal formation is critically involved in learning and memory and contains a large proportion of neurons encoding aspects of the organism's spatial surroundings. In the medial entorhinal cortex (MEC), this includes grid cells with their distinctive hexagonal firing fields as well as a host of other functionally defined cell types including head direction cells, speed cells, border cells, and object-vector cells. Such spatial coding emerges from the processing of external inputs by local microcircuits. However, it remains unclear exactly how local microcircuits and their dynamics within the MEC contribute to spatial discharge patterns. In this review we focus on recent investigations of intrinsic MEC connectivity, which have started to describe and quantify both excitatory and inhibitory wiring in the superficial layers of the MEC. Although the picture is far from complete, it appears that these layers contain robust recurrent connectivity that could sustain the attractor dynamics posited to underlie grid pattern formation. These findings pave the way to a deeper understanding of the mechanisms underlying spatial navigation and memory.
21 citations
TL;DR: This new validated and automatic locomotion state‐detection method enables fast and reliable state‐specific analysis facilitating discovery of state‐dependent drug‐effects and control for altered occurrence of locomotion.
Abstract: Quantitative electroencephalography from freely moving rats is commonly used as a translational tool for predicting drug-effects in humans. We hypothesized that drug-effects may be expressed differently depending on whether the rat is in active locomotion or sitting still during recording sessions, and proposed automatic state-detection as a viable tool for estimating drug-effects free of hypo-/hyperlocomotion-induced effects. We aimed at developing a fully automatic and validated method for detecting two behavioural states: active and inactive, in one-second intervals and to use the method for evaluating ketamine, DOI, d-cycloserine, d-amphetamine, and diazepam effects specifically within each state. The developed state-detector attained high precision with more than 90% of the detected time correctly classified, and multiple differences between the two detected states were discovered. Ketamine-induced delta activity was found specifically related to locomotion. Ketamine and DOI suppressed theta and beta oscillations exclusively during inactivity. Characteristic gamma and high-frequency oscillations (HFO) enhancements of the NMDAR and 5HT2A modulators, speculated associated with locomotion, were profound and often largest during the inactive state. State-specific analyses, theoretically eliminating biases from altered occurrence of locomotion, revealed only few effects of d-amphetamine and diazepam. Overall, drug-effects were most abundant in the inactive state. In conclusion, this new validated and automatic locomotion state-detection method enables fast and reliable state-specific analysis facilitating discovery of state-dependent drug-effects and control for altered occurrence of locomotion. This may ultimately lead to better cross-species translation of electrophysiological effects of pharmacological modulations.
21 citations
Cites background from "NMDA receptor-dependent switching b..."
...Gamma rhythms have been found mediated by interneurons (Buzsáki & Wang, 2012) with peak- frequency depending on NMDAR activity at least in entorhinal cortex (Middleton et al., 2008)....
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TL;DR: A set of gamma oscillations that differentially regulate neuronal activity in the dentate gyrus and CA1 area, and may allow flexible segregation and integration of information across different levels of hippocampal circuitry are disclosed.
Abstract: The molecular layer of the dentate gyrus and the anatomically adjacent stratum lacunosum-moleculare of CA1 area, represent afferent areas at distinct levels of the hippocampal trisynaptic loop. Afferents to the dentate gyrus and CA1 area originate from different cell populations, including projection cells in entorhinal cortex layers two and three, respectively. To determine the organization of oscillatory activities along these terminal fields, we recorded local field potentials from multiple sites in the dentate gyrus and CA1 area of the awake mice, and localized gamma frequency (30-150 Hz) oscillations in different layers by means of current source density analysis. During theta oscillations, we observed different temporal and spectral organization of gamma oscillations in the dendritic layers of the dentate gyrus and CA1 area, with a sharp transition across the hippocampal fissure. In CA1 stratum lacunosum-moleculare, transient mid-frequency gamma oscillations (CA1-gammaM; 80 Hz) occurred on theta cycle peaks, while in the dentate gyrus, fast (DG-gammaF; 110 Hz), and slow (DG-gammaS; 40 Hz) gamma oscillations preferentially occurred on troughs of theta waves. Units in dentate gyrus, in contrast to units in CA1 pyramidal layer, phase-coupled to DG-gammaF, which was largely independent from CA1 fast gamma oscillations (CA1-gammaF) of similar frequency and timing. Spike timing of units recorded in either CA1 area or dentate gyrus were modulated by CA1-gammaM. Our experiments disclosed a set of gamma oscillations that differentially regulate neuronal activity in the dentate gyrus and CA1 area, and may allow flexible segregation and integration of information across different levels of hippocampal circuitry.
21 citations
Cites background from "NMDA receptor-dependent switching b..."
...…for such entrainment include the GABAergic back-projection from CA1 to the DG (Katona et al. 2016; Klausberger et al. 2005; Fuentealba et al. 2010) or the entrainment of L2 network by L3 cells at theta peaks in the absence of its intrinsic rhythm as observed in vitro (Middleton et al. 2008)....
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...Indeed, when rhythmically excited at theta frequency in vitro, the L2 microcircuit of the mEC (including stellate cells and mutually connected GABAergic basket cells) generates transient synchronous gamma oscillations at every theta cycle, even when its L3 afferents are severed (Pastoll et al. 2013; Middleton et al. 2008; Couey et al. 2013), pointing to the PP as a potential source of DG-gammaF....
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...Stellate cells, together with GABAergic L2 basket cells, form a microcircuit capable of autonomously generating powerful theta-nested gamma oscillations independent of the L3, in vitro (Pastoll et al. 2013; Middleton et al. 2008; Couey et al. 2013)....
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...…stellate cells and mutually connected GABAergic basket cells) generates transient synchronous gamma oscillations at every theta cycle, even when its L3 afferents are severed (Pastoll et al. 2013; Middleton et al. 2008; Couey et al. 2013), pointing to the PP as a potential source of DG-gammaF....
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TL;DR: It is proposed that sequential approximately 10 Hz clustered activation of the local hippocampal circuit occurring under the dynamics of SPWs and depending on NMDA receptors and an accurate level of GABAergic synaptic transmission is an essential pattern of precisely controlled network activity involved in synaptic plasticity processes with potential implications in mnemonic functions.
19 citations
01 Jan 2017
TL;DR: It is suggested that oscillating neuronal populations can support either response selection (routing) or combination, depending on the interplay between the kinetics of synaptic inhibition and the degree of heterogeneity of principal cell intrinsic conductances.
Abstract: The anterior cingulate cortex (ACC) is vital for a range of brain functions requiring cognitive control and has highly divergent inputs and outputs, thus manifesting as a hub in connectomic analyses. Studies show diverse functional interactions within the ACC are associated with network oscillations in the β (20-30 Hz) and γ (30-80 Hz) frequency range. Oscillations permit dynamic routing of information within cortex, a function that depends on bandpass filter-like behavior to selectively respond to specific inputs. However, a putative hub region such as ACC needs to be able to combine inputs from multiple sources rather than select a single input at the expense of others. To address this potential functional dichotomy, we modeled local ACC network dynamics in the rat in vitro. Modal peak oscillation frequencies in the β- and γ-frequency band corresponded to GABAAergic synaptic kinetics as seen in other regions; however, the intrinsic properties of ACC principal neurons were highly diverse. Computational modeling predicted that this neuronal response diversity broadened the bandwidth for filtering rhythmic inputs and supported combination-rather than selection-of different frequencies within the canonical γ and β electroencephalograph bands. These findings suggest that oscillating neuronal populations can support either response selection (routing) or combination, depending on the interplay between the kinetics of synaptic inhibition and the degree of heterogeneity of principal cell intrinsic conductances.
18 citations
Cites background from "NMDA receptor-dependent switching b..."
...In the case of oscillations, frequency can vary as much as 20 Hz depending on the region of origin (Middleton et al., 2008; Herrmann et al., 2010) and the properties of the sensory input that generates them (Orekhova et al., 2015; Perry et al., 2015)....
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...In the case of oscillations, frequency can vary as much as 20 Hz depending on the region of origin (Middleton et al., 2008; Herrmann et al., 2010) and the properties of the sensory input that generates them (Orekhova et al....
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References
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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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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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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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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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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