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, the authors presented a systematic pipeline to produce first-approximation estimates for most of the missing information, including connection probabilities and number of contacts for >1900 neuron type pairs.
Abstract: A quantitative description of the hippocampal formation synaptic architecture is essential for understanding the neural mechanisms of episodic memory. Yet the existing knowledge of connectivity statistics between different neuron types in the rodent hippocampus only captures a mere 5% of this circuitry. We present a systematic pipeline to produce first-approximation estimates for most of the missing information. Leveraging the www.Hippocampome.org knowledge base, we derive local connection parameters between distinct pairs of morphologically identified neuron types based on their axonal-dendritic overlap within every layer and subregion of the hippocampal formation. Specifically, we adapt modern image analysis technology to determine the parcel-specific neurite lengths of every neuron type from representative morphologic reconstructions obtained from either sex. We then compute the average number of synapses per neuron pair using relevant anatomic volumes from the mouse brain atlas and ultrastructurally established interaction distances. Hence, we estimate connection probabilities and number of contacts for >1900 neuron type pairs, increasing the available quantitative assessments more than 11-fold. Connectivity statistics thus remain unknown for only a minority of potential synapses in the hippocampal formation, including those involving long-range (23%) or perisomatic (6%) connections and neuron types without morphologic tracings (7%). The described approach also yields approximate measurements of synaptic distances from the soma along the dendritic and axonal paths, which may affect signal attenuation and delay. Overall, this dataset fills a substantial gap in quantitatively describing hippocampal circuits and provides useful model specifications for biologically realistic neural network simulations, until further direct experimental data become available.SIGNIFICANCE STATEMENT The hippocampal formation is a crucial functional substrate for episodic memory and spatial representation. Characterizing the complex neuron type circuit of this brain region is thus important to understand the cellular mechanisms of learning and navigation. Here we present the first numerical estimates of connection probabilities, numbers of contacts per connected pair, and synaptic distances from the soma along the axonal and dendritic paths, for more than 1900 distinct neuron type pairs throughout the dentate gyrus, CA3, CA2, CA1, subiculum, and entorhinal cortex. This comprehensive dataset, publicly released online at www.Hippocampome.org, constitutes an unprecedented quantification of the majority of the local synaptic circuit for a prominent mammalian neural system and provides an essential foundation for data-driven, anatomically realistic neural network models.

17 citations

Journal ArticleDOI
TL;DR: High-frequency hypersynchronization following NMDAr blockade occurring in cortical slices suggests that-at least part of-the underlying mechanisms of this schizophrenia feature persist in the local cortical circuit, even in the absence of long-range cortical or subcortical inputs.

15 citations

Journal ArticleDOI
TL;DR: The study identifies 2 subcircuits within the entorhinal cortex (EC) that are capable of generating gamma oscillations at different frequencies and points out for the first time the specialized role of inhibitory interneuron types in generating oscillatory patterns at different frequency.
Abstract: Neuronal networks in the brain oscillate in various frequency bands, and such oscillations can be detected by observing local field potential or EEG activity (1). Oscillations in the gamma frequency band (30–80 Hz) have drawn special attention because of their link to a variety of cognitive processes including sensory binding (2), attention selection (3), and memory (4, 5). Of particular physiological interest are questions of how gamma oscillations are generated and synchronized across brain regions. The study by Middleton et al. in this issue of PNAS (6) provides novel insights into these questions: it identifies 2 subcircuits within the entorhinal cortex (EC) that are capable of generating gamma oscillations at different frequencies. Moreover, it presents data implying that these generators recruit different neuronal pathways in their communication with the hippocampus. Their study points out for the first time the specialized role of inhibitory interneuron types in generating oscillatory patterns at different frequencies. Given that both the hippocampo–EC system and gamma oscillations are linked to memory processing, the temporal interactions between the EC and the hippocampus at these distinct gamma frequencies could be involved in different aspects of mnemonic processes.

14 citations


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

  • ...’s study (6) proposes that NMDAR activation could control the nature of the temporal interaction between the EC and the hippocampus by switching from one gamma pattern to another....

    [...]

  • ...In the absence of NMDAR-mediated excitation, the spiking activity of basket cells is reduced, releasing goblet cells to interact with principal cells. www.pnas.org cgi doi 10.1073 pnas.0810064105 PNAS November 25, 2008 vol. 105 no. 47 18079–18080 C O M M E N T A R Y a result predicted by modeling work (8–12)....

    [...]

  • ...study (6) shows that hippocampal regions in vitro have a selective preference for slow or fast gamma oscillations: whereas the CA1 region preferentially oscillates with 40-Hz oscillations, the CA3 region prefers slower 30-Hz oscillations....

    [...]

  • ...in this issue of PNAS (6) provides novel insights into these questions: it identifies 2 subcircuits within the entorhinal cortex (EC) that are capable of generating gamma oscillations at different frequencies....

    [...]

  • ...(6) and their differential communication with the CA3 and CA1 regions could support the 2 forms of coding observed....

    [...]

Journal ArticleDOI
TL;DR: The results indicate that the intracellular kinases Akt and GSk3β play a critical role in the ethanol-induced suppression of γ oscillations and reveal new cellular pathways involved in the alcohol-induced cognitive impairment.
Abstract: Hippocampal network oscillations at gamma band frequency (γ, 30-80 Hz) are closely associated with higher brain functions such as learning and memory. Acute ethanol exposure at intoxicating concentrations (≥50mM) impairs cognitive function. This study aimed to determine the effects and the mechanisms of acute ethanol exposure on γ oscillations in an in vitro model. Ethanol (25-100 mM) suppressed kainate-induced γ oscillations in CA3 area of the rat hippocampal slices, in a concentration-dependent, reversible manner. The ethanol-induced suppression was reduced by the D1R antagonist SCH23390 or the PKA inhibitor H89, was prevented by the Akt inhibitor Triciribine or the GSk3β inhibitor SB415286, was enhanced by the NMDA receptor antagonist D-AP5, but was not affected by the MAPK inhibitor U0126 or PI3K inhibitor wortmanin. Our results indicate the intracellular kinases Akt and GSk3β play a critical role in the ethanol-induced suppression of γ oscillations and reveal new cellular pathways involved in the ethanol-induced cognitive impairment.

14 citations


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

  • ...However, NMDAR blockade enhances the ethanol-induced suppression of γ, which may be associated with the contribution of NMDAR to the tonic drive of interneurons (Middleton et al., 2008; Mann and Mody, 2010; Xue et al., 2011)....

    [...]

Book ChapterDOI
01 Jan 2010
TL;DR: This chapter is to summarize recent findings from different laboratories' works in in vitro preparations highlighting the importance of different neuronal activity patterns of hippocampal principal cells and different subtypes of interneurons during network oscillations.
Abstract: Neurons form transient, functionally specialized assemblies by coordinating their activity within networks. Assembly activity is important for coding and information processing in the brain; oscillations are assumed to entrain and provide temporal structure to this. Recent work from different laboratories has uncovered cell type-specific activity patterns during network oscillations, indicating that the cells may differentially contribute to the generation of oscillation and thereby the coordination of cell assemblies. The purpose of this chapter is to summarize recent findings from these works in in vitro preparations highlighting the importance of different neuronal activity patterns of hippocampal principal cells and different subtypes of interneurons. Special attention will be paid to the role of the firing properties of hippocampal interneurons on the network oscillatory activity at the theta and gamma frequency range. Models based on these ideas are found in “Gamma and Theta Rhythms in Biophysical Models of Hippocampal Circuits” by Kopell et al., this book.

13 citations


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

  • ...In line with this suggestion, both persistent and transient forms of kainate-induced gamma oscillations demonstrate faster gamma frequency oscillations in isolated CA1 area than those in CA3 area (N. Maziashvili and T. Gloveli, unpublished observation, Middleton et al., 2008)....

    [...]

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