scispace - formally typeset
Search or ask a question
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.

Content maybe subject to copyright    Report

Citations
More filters
Journal ArticleDOI
TL;DR: In this article, a hippocampal-entorhinal cortical (EC) network model was proposed to explore the mechanism of epileptic generation and demonstrated that enhanced excitability of pyramidal neurons in cornu ammonis 3 (CA3) can drive hippocampal EC to produce a transition from background to seizure state and cause exaggerated phase-amplitude coupling (PAC) phenomenon of theta modulated high-frequency oscillations (HFO) in CA3, cornU ammonis 1 (CA1), dentate gyrus, and EC.
Abstract: Temporal lobe epilepsy (TLE) is thought to be associated with neuronal hyperexcitability in the hippocampal-entorhinal cortical (EC) circuit. Due to the complexity of the hippocampal-EC network connections, the biophysical mechanisms of the different circuits in epilepsy generation and propagation are still not fully established. In this work, we propose a hippocampal-EC neuronal network model to explore the mechanism of epileptic generation. We demonstrate that enhanced excitability of pyramidal neurons in cornu ammonis 3 (CA3) can drive hippocampal-EC to produce a transition from background to seizure state and cause exaggerated phase-amplitude coupling (PAC) phenomenon of theta modulated high-frequency oscillations (HFO) in CA3, cornu ammonis 1 (CA1), dentate gyrus, and EC. Interestingly, PAC strength indirectly responds to the degree of CA3 pyramidal (PY) neuron hyperexcitability, suggesting that PAC can be used as a potential marker of seizures. Furthermore, we find that enhanced synaptic connectivity of mossy cells to granule cells and CA3 PY neurons drives the system to produce epileptic discharges. These two channels may play a key role in mossy fiber sprouting. In particular, the PAC phenomenon of delta-modulated HFO and theta-modulated HFO can be generated according to the different degrees of moss fiber sprouting. Finally, the results suggest that hyperexcitability of stellate cells in EC can lead to seizures, which supports the argument that EC can act as an independent source of seizures. Overall, these results highlight the key role of different circuits in seizures, providing a theoretical basis and new insights into the generation and propagation of TLE.

1 citations

01 Jan 2009

1 citations


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

  • ...However, research seems to suggest that differences in frequencies associated with various mechanisms may indeed be important for determining which pathways are most effective under particular circumstances (Middleton et al., 2008)....

    [...]

Dissertation
01 Jan 2015
TL;DR: This work presents evidence for a differential role of the DP and the underlying dorsal tenia tecta in the brain of the rat medial prefrontal cortex and investigates the role of dopamine in this role in animals and humans.
Abstract: .......................................................................................................................... ii Acknowledgements ........................................................................................................ iii Publications ..................................................................................................................... v Table of contents ............................................................................................................ vi List of figures ................................................................................................................... x List of tables ................................................................................................................. xiv List of abbreviations ..................................................................................................... xv Chapter 1. General introduction ................................................................................... 1 1.1 The mammalian prefrontal cortex ...................................................................... 1 1.2 The rat medial prefrontal cortex ......................................................................... 4 1.2.1 Location and functional homology with the human brain ............................... 4 1.2.2 Laminar structure defines mPFC sub-regions ................................................. 4 1.2.3 Connectivity of mPFC sub-regions ................................................................. 5 1.2.4 Functions of mPFC sub-regions ...................................................................... 5 1.2.5 A dorsal-to-ventral division of the mPFC ....................................................... 8 1.2.6 Evidence for a differential role of the DP and the underlying dorsal tenia tecta ........................................................................................................................... 8 1.3 Brain rhythms during wakefulness in the prefrontal cortex ............................ 8 1.4 Sleep and associated brain rhythms .................................................................. 10 1.4.1 Sleep stages .................................................................................................... 10 1.4.2 Discovery of cortical slow wave activity (SWA) .......................................... 12 1.4.3 Occurrence of SWA/UDS .............................................................................. 13 1.4.4 UDS – cortical or thalamic origin? ................................................................ 13 1.4.5 The three-oscillator model of UDS ................................................................ 14 1.4.6 SWA as a travelling wave .............................................................................. 17 1.4.7 Slow waves and nested oscillations ............................................................... 18 1.4.8 Function of SWA ........................................................................................... 22 1.4.9 Function of nested fast oscillations during SWA .......................................... 25 1.5 Dopamine ............................................................................................................. 27 1.5.1 Dopamine pathways of the brain ................................................................... 27 1.5.2 Projections from the VTA to the mPFC ........................................................ 28 1.5.3 Dopamine receptors ....................................................................................... 28 1.5.4 Effects of dopamine in the brain .................................................................... 29 1.5.5 PFC functions regulated by dopamine ........................................................... 32 1.5.6 Features of dopamine action .......................................................................... 33 1.5.7 Dopamine disorders and sleep disturbances .................................................. 33 1.6 Thesis overview ................................................................................................... 34 Chapter 2. Methods ...................................................................................................... 35 2.1 Animals ................................................................................................................ 35 2.2 Electrophysiological recordings under anaesthesia ......................................... 35 2.2.1 Anaesthesia .................................................................................................... 35 2.2.2 Surgery ........................................................................................................... 35 2.2.3 Recording electrodes and coordinates ........................................................... 36 2.2.4 Data acquisition ............................................................................................. 37 2.2.5 Histological verification of recording site position ....................................... 39 2.3 Experimental interventions ................................................................................ 43

1 citations


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

  • ...7, PV interneurons are strongly implicated in the generation of cortical gamma rhythms (Fuchs et al., 2007; Middleton et al., 2008; Cardin et al., 2009; Sohal et al., 2009; Carlen et al., 2012)....

    [...]

  • ...As already discussed in section 1.4.7, PV+ interneurons are strongly implicated in the generation of cortical gamma rhythms (Fuchs et al., 2007; Middleton et al., 2008; Cardin et al., 2009; Sohal et al., 2009; Carlen et al., 2012)....

    [...]

  • ...The involvement of a specific class of inhibitory interneurons, which expresses the Ca2+ buffer parvalbumin (PV), has been indicated (Fuchs et al., 2007; Middleton et al., 2008; Carlen et al., 2012) and confirmed using optogenetics (Cardin et al., 2009; Sohal et al., 2009)....

    [...]

  • ...The involvement of a specific class of inhibitory interneurons, which expresses the Ca buffer parvalbumin (PV), has been indicated (Fuchs et al., 2007; Middleton et al., 2008; Carlen et al., 2012) and confirmed using optogenetics (Cardin et al....

    [...]

Dissertation
01 Feb 2017
TL;DR: It is suggested that greater synaptic plasticity occurring in the whole network due to increase in reception of external excitatory inputs makes the network more susceptible to generation of epileptic activity.
Abstract: Temporal lobe epilepsy (TLE) is a common type of epilepsy with hippocampus as the usual site of origin. The CA3 subfield of hippocampus is reported to have a low epileptic threshold and hence initiates the disorder in patients with TLE. This study computationally investigates how impaired dendritic inhibition of pyramidal cells in the vulnerable CA3 subfield leads to generation of epileptic activity. A model of CA3 subfield consisting of 800 pyramidal cells, 200 basket cells (BC) and 200 Oriens—Lacunosum Moleculare (O-LM) interneurons was used. The dendritic inhibition provided by O-LM interneurons is reported to be selectively impaired in some TLEs. A step-wise approach is taken to investigate how alterations in network connectivity lead to generation of epileptic patterns. Initially, dendritic inhibition alone was reduced, followed by an increase in the external inputs received at the distal dendrites of pyramidal cells, and finally additional changes were made at the synapses between all neurons in the network. In the first case, when the dendritic inhibition of pyramidal cells alone was reduced, the local field potential activity changed from a thetamodulated gamma pattern to a prominently gamma frequency pattern. In the second case, in addition to this reduction of dendritic inhibition, with a simultaneous large increase in the external excitatory inputs received by pyramidal cells, the basket cells entered a state of depolarization block, causing the network to generate a typical ictal activity pattern. In the third case, when the dendritic inhibition onto the pyramidal cells was reduced and changes were simultaneously made in synaptic connectivity between all neurons in the network, the basket cells were again observed to enter depolarization block. In the third case, impairment of dendritic inhibition required to generate an ictal activity pattern was lesser than the two previous cases. Moreover, the ictal like activity began earlier in the third case. Hence, our study suggests that greater synaptic plasticity occurring in the whole network due to increase in reception of external excitatory inputs (due to impaired dendritic inhibition) makes the network more susceptible to generation of epileptic activity. VC 2015 Wiley Periodicals, Inc.
Dissertation
25 Sep 2015
TL;DR: Results from the study of co-agonist site ligands provide important new insights into the relationship between NMDA receptors and neuronal synchrony and also the mechanism of cognitive enhancement by the high efficacy partial co-agonists D-Cycloserine.
Abstract: The NMDA receptor is a highly diverse receptor with many functions. In particular NMDA receptors present on postsynaptic spines mediate the effects of the synaptic neurotransmitter glutamate, whilst NMDA receptors present on presynaptic nerve terminals directly regulate the release of neurotransmitters. The aim of this thesis was to expand the characterisation of these two populations of NMDA receptors by examining the functional role of the co-agonist binding sites. NMDA receptors have been strongly implicated in mechanisms of cognition and also the pathophysiology epilepsy and so I have focused my study in the entorhinal cortex which is an area increasingly seen to be central to both of these phenomenon. Initial work focussed on the endogenous regulation of the presynaptic NMDA receptors. My results indicated that the co-agonist site of these receptors was activated by D-serine and that this ligand may come from astrocytes, in contrast to the observations that others have made for postsynaptic NMDA receptors. Following this, I then characterised the effects of partial agonists of the NMDA receptor co-agonist site at each of these populations of NMDA receptors and report differential effects for the function of these receptors. Finally I then examined the effects of the co-agonist site ligands on epileptiform activity as a simple form of emergent neuronal network activity. Results from my study of co-agonist site ligands provide important new insights into the relationship between NMDA receptors and neuronal synchrony and also the mechanism of cognitive enhancement by the high efficacy partial co-agonist D-Cycloserine.
References
More filters
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)....

    [...]

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)....

    [...]

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)....

    [...]

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