Deficient GABAergic Gliotransmission May Cause Broader Sensory Tuning in Schizophrenia

2013 ◽  
Vol 25 (12) ◽  
pp. 3235-3262 ◽  
Author(s):  
Osamu Hoshino
Keyword(s):  
Glial Cell ◽  
Glial Cells ◽  
Extracellular Space ◽  
Regulatory Mechanism ◽  
Intracortical Inhibition ◽  
Gaba Concentration ◽  
Principal Cells ◽  
Dynamic Cell ◽  
Ambient Gaba ◽  
Feature Stimulus

We examined how the depression of intracortical inhibition due to a reduction in ambient GABA concentration impairs perceptual information processing in schizophrenia. A neural network model with a gliotransmission-mediated ambient GABA regulatory mechanism was simulated. In the network, interneuron-to-glial-cell and principal-cell-to-glial-cell synaptic contacts were made. The former hyperpolarized glial cells and let their transporters import (remove) GABA from the extracellular space, thereby lowering ambient GABA concentration, reducing extrasynaptic GABAa receptor-mediated tonic inhibitory current, and thus exciting principal cells. In contrast, the latter depolarized the glial cells and let the transporters export GABA into the extracellular space, thereby elevating the ambient GABA concentration and thus inhibiting the principal cells. A reduction in ambient GABA concentration was assumed for a schizophrenia network. Multiple dynamic cell assemblies were organized as sensory feature columns. Each cell assembly responded to one specific feature stimulus. The tuning performance of the network to an applied feature stimulus was evaluated in relation to the level of ambient GABA. Transporter-deficient glial cells caused a deficit in GABAergic gliotransmission and reduced ambient GABA concentration, which markedly deteriorated the tuning performance of the network, broadening the sensory tuning. Interestingly, the GABAergic gliotransmission mechanism could regulate local ambient GABA levels: it augmented ambient GABA around stimulus-irrelevant principal cells, while reducing ambient GABA around stimulus-relevant principal cells, thereby ensuring their selective responsiveness to the applied stimulus. We suggest that a deficit in GABAergic gliotransmission may cause a reduction in ambient GABA concentration, leading to a broadening of sensory tuning in schizophrenia. The GABAergic gliotransmission mechanism proposed here may have an important role in the regulation of local ambient GABA levels, thereby improving the sensory tuning performance of the cortex.

Regulation of Ambient GABA Levels by Neuron-Glia Signaling for Reliable Perception of Multisensory Events

2012 ◽  
Vol 24 (11) ◽  
pp. 2964-2993 ◽  
Author(s):  
Osamu Hoshino
Keyword(s):  
Glial Cells ◽  
Extracellular Space ◽  
Sensory Modality ◽  
Gabaergic Interneuron ◽  
Gain Function ◽  
Principal Cells ◽  
Ambient Gaba ◽  
The Cross ◽  
Multisensory Information ◽  
Stimulation Of

Activities of sensory-specific cortices are known to be suppressed when presented with a different sensory modality stimulus. This is referred to as cross-modal inhibition, for which the conventional synaptic mechanism is unlikely to work. Interestingly, the cross-modal inhibition could be eliminated when presented with multisensory stimuli arising from the same event. To elucidate the underlying neuronal mechanism of cross-modal inhibition and understand its significance for multisensory information processing, we simulated a neural network model. Principal cell to and GABAergic interneuron to glial cell projections were assumed between and within lower-order unimodal networks (X and Y), respectively. Cross-modality stimulation of Y network activated its principal cells, which then depolarized glial cells of X network. This let transporters on the glial cells export GABA molecules into the extracellular space and increased a level of ambient (extrasynaptic) GABA. The ambient GABA molecules were accepted by extrasynaptic GABAa receptors and tonically inhibited principal cells of the X network. Cross-modal inhibition took place in a nonsynaptic manner. Identical modality stimulation of X network activated its principal cells, which then activated interneurons and hyperpolarized glial cells of the X network. This let their transporters import (remove) GABA molecules from the extracellular space and reduced tonic inhibitory current in principal cells, thereby improving their gain function. Top-down signals from a higher-order multimodal network (M) contributed to elimination of the cross-modal inhibition when presented with multisensory stimuli that arose from the same event. Tuning into the multisensory event deteriorated if the cross-modal inhibitory mechanism did not work. We suggest that neuron-glia signaling may regulate local ambient GABA levels in order to coordinate cross-modal inhibition and improve neuronal gain function, thereby achieving reliable perception of multisensory events.

Facilitation of Neuronal Responses by Intrinsic Default Mode Network Activity

2014 ◽  
Vol 26 (11) ◽  
pp. 2441-2464 ◽  
Author(s):  
Hiroakira Matsui ◽  
Meihong Zheng ◽  
Osamu Hoshino
Keyword(s):  
Glial Cells ◽  
Default Mode Network ◽  
Network Activity ◽  
Gaba Concentration ◽  
Default Mode ◽  
Model Network ◽  
Principal Cells ◽  
Ambient Gaba ◽  
Glial Membrane ◽  
Reaction Speed

Default mode network (DMN) shows intrinsic, high-level activity at rest. We tested a hypothesis proposed for its role in sensory information processing: Intrinsic DMN activity facilitates neural responses to sensory input. A neural network model, consisting of a sensory network (Nsen) and a DMN, was simulated. The Nsen contained cell assemblies. Each cell assembly comprised principal cells, GABAergic interneurons (Ia, Ib), and glial cells. We let the Nsen carry out a perceptual task: detection of sensory stimuli. During DMN activation, glial cells were hyperpolarized by Ia-to-glia circuitry, by which glial membrane transporters imported GABA molecules from the extracellular space and decreased ambient GABA concentration. Acting on extrasynaptic GABA receptors, the decrease in ambient GABA concentration reduced inhibitory current in a tonic manner. This depolarized principal cells below their firing threshold during the ongoing spontaneous time period and accelerated their reaction speed to a sensory stimulus. During the stimulus presentation period, the Nsen inhibited the DMN and caused DMN deactivation. The DMN deactivation made Nsen Ia cells cease firing, thereby stopping the glial membrane hyperpolarization, quitting the GABA import, returning to the basal ambient GABA level, and thus enhancing global inhibition. Notably, the stimulus-relevant P cell firing could be maintained when GABAergic gliotransmission via Ia-glia signaling worked, decreasing ambient GABA concentration around the stimulus-relevant P cells. This enabled the Nsen to reliably detect the stimulus. We suggest that intrinsic default model network activity may accelerate the reaction speed of the sensory network by modulating its ongoing-spontaneous activity in a subthreshold manner. Ambient GABA contributes to achieve an optimal ongoing spontaneous subthreshold neuronal state, in which GABAergic gliotransmission triggered by the intrinsic default model network activity may play an important role.

Reduction of Trial-to-Trial Perceptual Variability by Intracortical Tonic Inhibition

2016 ◽  
Vol 28 (1) ◽  
pp. 187-215 ◽  
Author(s):  
Osamu Hoshino ◽  
Meihong Zheng ◽  
Kazuo Watanabe
Keyword(s):  
Neuronal Activity ◽  
Network Model ◽  
Dependent Manner ◽  
Gaba Concentration ◽  
Cell Assemblies ◽  
Principal Cells ◽  
Ambient Gaba ◽  
Spontaneous Neuronal Activity ◽  
Perceptual Variability ◽  
Feature Stimulus

Variability is a prominent characteristic of cognitive brain function. For instance, different trials of presentation of the same stimulus yield higher variability in its perception: subjects sometimes fail in perceiving the same stimulus. Perceptual variability could be attributable to ongoing-spontaneous fluctuation in neuronal activity prior to sensory stimulation. Simulating a cortical neural network model, we investigated the underlying neuronal mechanism of perceptual variability in relation to variability in ongoing-spontaneous neuronal activity. In the network model, populations of principal cells (cell assemblies) encode information about sensory features. Each cell assembly is sensitive to one particular feature stimulus. Transporters on GABAergic interneurons regulate ambient GABA concentration in a neuronal activity-dependent manner. Ambient GABA molecules activate extrasynaptic GABA[Formula: see text] receptors on principal cells and interneurons, and provide them with tonic inhibitory currents. We controlled the variability of ongoing-spontaneous neuronal activity by manipulating the basal level of ambient GABA and assessed the perceptual performance of the network: detection of a feature stimulus. In an erroneous response, stimulus-irrelevant but not stimulus-relevant principal cells were activated, generating trains of action potentials. Perceptual variability, reflected in error rate in detecting the same stimulus that was presented repeatedly to the network, was increased as the variability in ongoing-spontaneous membrane potential among cell assemblies increased. Frequent, transient membrane depolarization below firing threshold was the major cause of the increased neuronal variability, for which a decrease in basal ambient GABA concentration was responsible. We suggest that ambient GABA in the brain may have a role in reducing the variability in ongoing-spontaneous neuronal activity, leading to a decrease in perceptual variability and therefore to reliable sensory perception.

Tonically Balancing Intracortical Excitation and Inhibition by GABAergic Gliotransmission

2014 ◽  
Vol 26 (8) ◽  
pp. 1690-1716 ◽  
Author(s):  
Meihong Zheng ◽  
Takami Matsuo ◽  
Ai Miyamoto ◽  
Osamu Hoshino
Keyword(s):  
Extracellular Space ◽  
Plasma Membranes ◽  
Sensory Information ◽  
Inhibitory Mechanism ◽  
Neuronal Responses ◽  
Gaba Concentration ◽  
Cell Assemblies ◽  
Gaba Transporters ◽  
Ambient Gaba ◽  
P Cells

For sensory cortices to respond reliably to feature stimuli, the balancing of neuronal excitation and inhibition is crucial. A typical example might be the balancing of phasic excitation within cell assemblies and phasic inhibition between cell assemblies. The former controls the gain of and the latter the tuning of neuronal responses. A change in ambient GABA concentration might affect the dynamic behavior of neurons in a tonic manner. For instance, an increase in ambient GABA concentration enhances the activation of extrasynaptic receptors, augments an inhibitory current, and thus inhibits neurons. When a decrease in ambient GABA concentration occurs, the tonic inhibitory current is reduced, and thus the neurons are relatively excited. We simulated a neural network model in order to examine whether and how such a tonic excitatory-inhibitory mechanism could work for sensory information processing. The network consists of cell assemblies. Each cell assembly, comprising principal cells (P), GABAergic interneurons (Ia, Ib), and glial cells (glia), responds to one particular feature stimulus. GABA transporters, embedded in glial plasma membranes, regulate ambient GABA levels. Hypothetical neuron-glia signaling via inhibitory (Ia-to-glia) and excitatory (P-to-glia) synaptic contacts was assumed. The former let transporters import (remove) GABA from the extracellular space and excited stimulus-relevant P cells. The latter let them export GABA into the extracellular space and inhibited stimulus-irrelevant P cells. The main finding was that the glial membrane transporter gave a combinatorial excitatory-inhibitory effect on P cells in a tonic manner, thereby improving the gain and tuning of neuronal responses. Interestingly, it worked cooperatively with the conventional, phasic excitatory-inhibitory mechanism. We suggest that the GABAergic gliotransmission mechanism may provide balanced intracortical excitation and inhibition so that the best perceptual performance of the cortex can be achieved.

scholarly journals The principal neurons of the medial nucleus of the trapezoid body and NG2+ glial cells receive coordinated excitatory synaptic input

2009 ◽  
Vol 134 (2) ◽  
pp. 115-127 ◽  
Author(s):  
Jochen Müller ◽  
Daniel Reyes-Haro ◽  
Tatjyana Pivneva ◽  
Christiane Nolte ◽  
Roland Schaette ◽  
...  
Keyword(s):  
Glial Cell ◽  
Glial Cells ◽  
Synaptic Input ◽  
Medial Nucleus ◽  
Synaptic Structure ◽  
Excitatory Synaptic Input ◽  
Cell Processes ◽  
To Receive ◽  
Trapezoid Body ◽  
Axosomatic Synapse

Glial cell processes are part of the synaptic structure and sense spillover of transmitter, while some glial cells can even receive direct synaptic input. Here, we report that a defined type of glial cell in the medial nucleus of the trapezoid body (MNTB) receives excitatory glutamatergic synaptic input from the calyx of Held (CoH). This giant glutamatergic terminal forms an axosomatic synapse with a single principal neuron located in the MNTB. The NG2 glia, as postsynaptic principal neurons, establish synapse-like structures with the CoH terminal. In contrast to the principal neurons, which are known to receive excitatory as well as inhibitory inputs, the NG2 glia receive mostly, if not exclusively, α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor–mediated evoked and spontaneous synaptic input. Simultaneous recordings from neurons and NG2 glia indicate that they partially receive synchronized spontaneous input. This shows that an NG2+ glial cell and a postsynaptic neuron share presynaptic terminals.

scholarly journals Far beyond the motor neuron: the role of glial cells in amyotrophic lateral sclerosis

2016 ◽  
Vol 74 (10) ◽  
pp. 849-854
Author(s):  
Paulo Victor Sgobbi de Souza ◽  
Wladimir Bocca Vieira de Rezende Pinto ◽  
Flávio Moura Rezende Filho ◽  
Acary Souza Bulle Oliveira
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Glial Cell ◽  
Glial Cells ◽  
Motor Neurons ◽  
Cell Interaction ◽  
Cell Functions ◽  
Glial Cell Interactions ◽  
Lateral Sclerosis

ABSTRACT Motor neuron disease is one of the major groups of neurodegenerative diseases, mainly represented by amyotrophic lateral sclerosis. Despite wide genetic and biochemical data regarding its pathophysiological mechanisms, motor neuron disease develops under a complex network of mechanisms not restricted to the unique functions of the alpha motor neurons but which actually involve diverse functions of glial cell interaction. This review aims to expose some of the leading roles of glial cells in the physiological mechanisms of neuron-glial cell interactions and the mechanisms related to motor neuron survival linked to glial cell functions.

scholarly journals Glial Purinergic Signaling in Neurodegeneration

2021 ◽  
Vol 12 ◽  
Author(s):  
Marie J. Pietrowski ◽  
Amr Ahmed Gabr ◽  
Stanislav Kozlov ◽  
David Blum ◽  
Annett Halle ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Glial Cell ◽  
Glial Cells ◽  
Purinergic Signaling ◽  
Expression Patterns ◽  
Specific Expression ◽  
Cell Functions ◽  
Signaling Components ◽  
Therapeutical Options

Purinergic signaling regulates neuronal and glial cell functions in the healthy CNS. In neurodegenerative diseases, purinergic signaling becomes dysregulated and can affect disease-associated phenotypes of glial cells. In this review, we discuss how cell-specific expression patterns of purinergic signaling components change in neurodegeneration and how dysregulated glial purinergic signaling and crosstalk may contribute to disease pathophysiology, thus bearing promising potential for the development of new therapeutical options for neurodegenerative diseases.

Some fly sensory organs are gliogenic and require glide/gcm in a precursor that divides symmetrically and produces glial cells

Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3735-3743 ◽  
Author(s):  
V. Van De Bor ◽  
R. Walther ◽  
A. Giangrande
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Glial Cell ◽  
Glial Cells ◽  
Sensory Organ ◽  
Asymmetric Distribution ◽  
Sensory Organs ◽  
The Central Nervous System ◽  
Glial Precursor

In flies, the choice between neuronal and glial fates depends on the asymmetric division of multipotent precursors, the neuroglioblast of the central nervous system and the IIb precursor of the sensory organ lineage. In the central nervous system, the choice between the two fates requires asymmetric distribution of the glial cell deficient/glial cell missing (glide/gcm) RNA in the neuroglioblast. Preferential accumulation of the transcript in one of the daughter cells results in the activation of the glial fate in that cell, which becomes a glial precursor. Here we show that glide/gcm is necessary to induce glial differentiation in the peripheral nervous system. We also present evidence that glide/gcm RNA is not necessary to induce the fate choice in the peripheral multipotent precursor. Indeed, glide/gcm RNA and protein are first detected in one daughter of IIb but not in IIb itself. Thus, glide/gcm is required in both central and peripheral glial cells, but its regulation is context dependent. Strikingly, we have found that only subsets of sensory organs are gliogenic and express glide/gcm. The ability to produce glial cells depends on fixed, lineage related, cues and not on stochastic decisions. Finally, we show that after glide/gcm expression has ceased, the IIb daughter migrates and divides symmetrically to produce several mature glial cells. Thus, the glide/gcm-expressing cell, also called the fifth cell of the sensory organ, is indeed a glial precursor. This is the first reported case of symmetric division in the sensory organ lineage. These data indicate that the organization of the fly peripheral nervous system is more complex than previously thought.

Sheaths of the Motor Axons of the Crab Carcinus

1964 ◽  
Vol s3-105 (70) ◽  
pp. 175-181
Author(s):  
G. A. HORRIDGE ◽  
R. A. CHAPMAN
Keyword(s):  
Cell Membrane ◽  
Glial Cell ◽  
Cross Section ◽  
Glial Cells ◽  
Fibrous Material ◽  
Motor Axons ◽  
Cell Cytoplasm ◽  
Fibrous Sheath ◽  
Outer Sheath ◽  
Sheath Structure

In crab leg nerves, the largest axons, which are the motor axons usually isolated for physiological experiments, have a sheath structure which is different from that in medium sized and smaller axons of the same nerve or of any other described nerves. Axons with a diameter over 20 µ have (a) an outer sheath, about 5µ thick, of wellspaced layers of alternating glial cell cytoplasm and extracellular fibrous material, formed from fewer cells than there are layers, and (b) an inner sheath of elongated cells which creep along the axon longitudinally and interdigitate where they meet, as seen 2 or 3 times round the outside of the membranes of axons in cross-section. Therefore, possible channels between inner glial cells are elongated and few. On these structural grounds, together with physiological evidence, they seem unlikely to be preferred pathways of diffusion of ions in crab axons. Smaller axons have simple sheaths; some occur in groups within a fibrous sheath; the thinnest axons frequently occur in bundles and have no glial cell membrane in contact with them.

scholarly journals Single-Cell RNA Sequencing in Human Retinal Degeneration Reveals Distinct Glial Cell Populations

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 438 ◽  
Author(s):  
Andrew P. Voigt ◽  
Elaine Binkley ◽  
Miles J. Flamme-Wiese ◽  
Shemin Zeng ◽  
Adam P. DeLuca ◽  
...  
Keyword(s):  
Single Cell ◽  
Retinal Degeneration ◽  
Rna Sequencing ◽  
Glial Cell ◽  
Glial Cells ◽  
Peripheral Retina ◽  
Cell Populations ◽  
Specific Gene ◽  
Autoimmune Retinopathy ◽  
Single Cell Rna Sequencing

Degenerative diseases affecting retinal photoreceptor cells have numerous etiologies and clinical presentations. We clinically and molecularly studied the retina of a 70-year-old patient with retinal degeneration attributed to autoimmune retinopathy. The patient was followed for 19 years for progressive peripheral visual field loss and pigmentary changes. Single-cell RNA sequencing was performed on foveal and peripheral retina from this patient and four control patients, and cell-specific gene expression differences were identified between healthy and degenerating retina. Distinct populations of glial cells, including astrocytes and Müller cells, were identified in the tissue from the retinal degeneration patient. The glial cell populations demonstrated an expression profile consistent with reactive gliosis. This report provides evidence that glial cells have a distinct transcriptome in the setting of human retinal degeneration and represents a complementary clinical and molecular investigation of a case of progressive retinal disease.

Sign in / Sign up

Export Citation Format

Share Document