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.
Citations
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TL;DR: Behind this known mechanism, there is a heterogeneity of GABAergic interneurons with distinct functions and sources, which have specific roles in controlling the neural network activity within the recruited microcircuit and altered network during the epileptogenic process.
38 citations
TL;DR: Arguments are reviewed that both subhypotheses 2 and 3 are, at present, unsatisfactory and the question that is addressed now is what is the validity of subhypothesis 1 and 2.
Abstract: In previous papers (Smythies et al., 2012, 2014) we presented the general hypothesis that the claustrum may be concerned with information processing operations on synchronized gamma oscillations in the brain at three levels. At the first level (subhypothesis 1) it just magnifies the oscillations in cortico-claustral circuits. At the second level (subhypothesis 2) it may integrate these oscillations. At the third level (subhypothesis 3) it might process the contained spike codes. These previous papers were concentrated upon the first level. In this paper we will review arguments that both subhypotheses 2 and 3 are, at present, unsatisfactory. Subhypothesis 1, however, remains satisfactory.
The claustrum consists of a body of densely interconnected P (pyramidal) cells and GABAergic interneurons (INs) arranged in a sheet of gray matter underlying the insula in the basal telencephalon of the mammalian brain. These cells are arranged in functional units, each of which is connected with a particular cortical or subcortical area with which the claustrum maintains reciprocal relationships, which encompass practically every such area. There is evidence that it is particularly concerned with salient activities requiring integration between two or more of these areas [see Smythies et al. (2012, 2014), for details]. One structurally facilitative feature of this anatomy is that the claustrum has a number of afferents/efferents along a topographical spectrum. There are well-defined arrays of visual-, auditory-, and somatosensory-associated zones (or “maps”), plus extensive limbic connections with the ventral claustrum. To the extent studied, individual P cells have been shown to receive a (mostly) modality-specific input. For example, visual zone neurons respond (almost) exclusively to visual stimuli, auditory neurons respond (almost) exclusively to auditory stimuli, etc. (Remedios et al., 2010). The afferent glutamatergic axons of cortical layer VI P cells densely synapse on claustral P cells. In turn, these claustral P cells reciprocate by sending efferents back to the very same cortical area from which their afferent input originated. It has been demonstrated that some claustral P cells have bifurcated axonal projections to different cortical areas. Of particular significance is that claustral P cells also maintain direct contact with claustral GABAergic INs via local collaterals forming a dense axonal array. The INs quite likely form an interactive gap-junction syncytium.
This structure entails that the afferent inflow to the claustrum will carry multiple impulses with different power spectra and synchronized at different frequencies that will have ample opportunity to interact in complex ways within the densely packed amorphous syncytium that constitutes the interior of the claustrum. The results of these interactions, in the form of processed and integrated information, might then be transported to selected areas of the brain via the efferent network. The question that we will address now is what is the validity of subhypotheses 2 and 3.
36 citations
TL;DR: It is found that activating acetylcholine receptors induced stable gamma oscillations in the CA1 local network isolated in slices in vitro that were faster than those in CA3, but relied on similar neuronal circuitry involving feedback inhibition.
Abstract: Hippocampal gamma oscillations have been associated with cognitive functions including navigation and memory encoding/retrieval. Gamma oscillations in area CA1 are thought to depend on the oscillatory drive from CA3 (slow gamma) or the entorhinal cortex (fast gamma). Here we show that the local CA1 network can generate its own fast gamma that can be suppressed by slow gamma-paced inputs from CA3. Moderate acetylcholine receptor activation induces fast (45 ± 1 Hz) gamma in rat CA1 minislices and slow (33 ± 1 Hz) gamma in CA3 minislices in vitro. Using pharmacological tools, current-source density analysis and intracellular recordings from pyramidal cells and fast-spiking stratum pyramidale interneurons, we demonstrate that fast gamma in CA1 is of the pyramidal-interneuron network gamma (PING) type, with the firing of principal cells paced by recurrent perisomal IPSCs. The oscillation frequency was only weakly dependent on IPSC amplitude, and decreased to that of CA3 slow gamma by reducing IPSC decay rate or reducing interneuron activation through tonic inhibition of interneurons. Fast gamma in CA1 was replaced by slow CA3-driven gamma in unlesioned slices, which could be mimicked in CA1 minislices by sub-threshold 35 Hz Schaffer collateral stimulation that activated fast-spiking interneurons but hyperpolarised pyramidal cells, suggesting that slow gamma frequency CA3 outputs can suppress the CA1 fast gamma-generating network by feed-forward inhibition and replaces it with a slower gamma oscillation driven by feed-forward inhibition. The transition between the two gamma oscillation modes in CA1 might allow it to alternate between effective communication with the medial entorhinal cortex and CA3, which have different roles in encoding and recall of memory.
36 citations
Cites background from "NMDA receptor-dependent switching b..."
...Fast gamma oscillations have previously been reported in CA1 minislices, induced by kainate or DHPG (Traub et al. 2003; Bibbig et al. 2007; Middleton et al. 2008; Kipiani, A B C D E F Figure 8....
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...…1995; Vreugdenhil et al. 2005) or focal application of micromolar kainate (Kipiani, 2009) in intact slices, or in isolated CA1 slices by very high concentrations of kainate (Traub et al. 2003; Middleton et al. 2008; Kipiani, 2009) or metabotropic glutamate receptor agonists (Bibbig et al. 2007)....
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...2005) or focal application of micromolar kainate (Kipiani, 2009) in intact slices, or in isolated CA1 slices by very high concentrations of kainate (Traub et al. 2003; Middleton et al. 2008; Kipiani, 2009) or metabotropic glutamate receptor agonists (Bibbig et al....
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TL;DR: The discovery of the pathways by which oxidative stress leads to unbalanced excitation and inhibition in cortical neural circuits opens a new perspective toward understanding the biological underpinnings of schizophrenia.
Abstract: Significance: Schizophrenia is a complex neuropsychiatric disorder affecting around 1% of the population worldwide. Its mode of inheritance suggests a multigenic neurodevelopmental disorder with symptoms appearing during late adolescence/early adulthood, with its onset strongly influenced by environmental stimuli. Many neurotransmitter systems, including dopamine, glutamate, and gamma-aminobutyric acid, show alterations in affected individuals, and the behavioral and physiological characteristics of the disease can be mimicked by drugs that produce blockade of N-methyl-d-aspartate glutamate receptors (NMDARs). Recent Advances: Mounting evidence suggests that drugs that block NMDARs specifically impair the inhibitory capacity of parvalbumin-expressing (PV+) fast-spiking neurons in adult and developing rodents, and alterations in these inhibitory neurons is one of the most consistent findings in the schizophrenic postmortem brain. Disruption of the inhibitory capacity of PV+ inhibitory neurons will...
35 citations
Cites background from "NMDA receptor-dependent switching b..."
...Amplitude of the gamma-rhythm was reported to increase in certain cortical regions, for example, the primary auditory cortex, as observed universally in vivo, but to significantly decrease in others, for example, the entorhinal cortex (45, 157, 190)....
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...Acute exposure to NMDAR antagonists in adults is believed to result in acute disinhibition (85, 140, 157, 177), as measured by increased excitatory activity in the frontal and anterior cingulate cortex (220)....
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TL;DR: Evidence is provided for a causal role for NMDA receptors in mediating spike pattern discriminability, neural plasticity, and rhythmic synchronization in relation to evaluative stimulus processing and decision making and illustrates how NMDAR blockade disrupts network dynamics.
35 citations
Cites background from "NMDA receptor-dependent switching b..."
...Slice studies further showed that NMDAR blockade increased the power of beta-band LFP oscillations in some areas (e.g., prelimbic and entorhinal cortex), but not in others (Middleton et al., 2008; Roopun et al., 2008)....
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..., prelimbic and entorhinal cortex), but not in others (Middleton et al., 2008; Roopun et al., 2008)....
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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