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.

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.

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.

Neuroscience of synesthesia and cross-modal associations

2014 ◽  
Vol 25 (6) ◽  
Author(s):  
Marcel Neckar ◽  
Petr Bob
Keyword(s):  
Current Knowledge ◽  
Sensory Modality ◽  
Subjective Experiences ◽  
Neural Basis ◽  
Behavioral Aspects ◽  
Stimulation Of

AbstractSynesthesia is a condition in which stimulation of one sensory modality causes unusual experiences in a different, unstimulated modality. Recent findings suggest that research on synesthesia offers a unique opportunity to study the neural basis of subjective experiences in healthy and pathological brains. This review summarizes and reflects current knowledge concerning synesthesia in its various aspects, including its cognitive, neural, and behavioral aspects. In this context, recent data suggest new connections between specific conditions related to synesthesic mechanisms and association processes linked to construction of synesthetic cross-modal metaphors that may play a role in psychopathological thinking and imagination.

scholarly journals Redistribution of alpha-granules and their contents in thrombin-stimulated platelets.

1984 ◽  
Vol 98 (2) ◽  
pp. 748-760 ◽  
Author(s):  
P E Stenberg ◽  
M A Shuman ◽  
S P Levine ◽  
D F Bainton
Keyword(s):  
Plasma Membrane ◽  
Tannic Acid ◽  
Extracellular Space ◽  
Plasma Membranes ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Thin Sections ◽  
Immunocytochemical Techniques ◽  
Morphologic Changes ◽  
Stimulation Of

The redistribution of beta-thromboglobulin (beta TG), platelet Factor 4 (PF4), and fibrinogen from the alpha granules of the platelet after stimulation with thrombin was studied by morphologic and immunocytochemical techniques. The use of tannic acid stain and quick-freeze techniques revealed several thrombin-induced morphologic changes. First, the normally discoid platelet became rounder in form, with filopodia, and the granules clustered in its center. The granules then fused with one another and with elements of the surface-connected canalicular system (SCCS) to form large vacuoles in the center of the cell and near the periphery. Neither these vacuoles nor the alpha granules appeared to fuse with the plasma membrane, but the vacuoles were connected to the extracellular space by wide necks, presumably formed by enlargement of the narrow necks connecting the SCCS to the surface of the unstimulated cell. The presence of fibrinogen, beta TG, and PF4 in corresponding large intracellular vacuoles and along the platelet plasma membrane after thrombin stimulation was demonstrated by immunocytochemical techniques in saponin-permeabilized and nonpermeabilized platelets. Immunocytochemical labeling of the three proteins on frozen thin sections of thrombin-stimulated platelets confirmed these findings and showed that all three proteins reached the plasma membrane by the same pathway. We conclude that thrombin stimulation of platelets causes at least some of the fibrinogen, beta TG, and PF4 stored in their alpha granules to be redistributed to their plasma membranes by way of surface-connected vacuoles formed by fusion of the alpha granules with elements of the SCCS.

scholarly journals Multimodal Medullary Neurons and Correlational Linkages of the Respiratory Network

1999 ◽  
Vol 82 (1) ◽  
pp. 188-201 ◽  
Author(s):  
Zhongzeng Li ◽  
Kendall F. Morris ◽  
David M. Baekey ◽  
Roger Shannon ◽  
Bruce G. Lindsey
Keyword(s):  
Firing Rate ◽  
Nucleus Tractus Solitarius ◽  
Motor Pattern ◽  
Sensory Modality ◽  
Spike Trains ◽  
Negative Feedback Regulation ◽  
Firing Rates ◽  
Respiratory Network ◽  
Cross Correlation Analysis ◽  
Stimulation Of

This study addresses the hypothesis that multiple sensory systems, each capable of reflexly altering breathing, jointly influence neurons of the brain stem respiratory network. Carotid chemoreceptors, baroreceptors, and foot pad nociceptors were stimulated sequentially in 33 Dial-urethan–anesthetized or decerebrate vagotomized adult cats. Neuronal impulses were monitored with microelectrode arrays in the rostral and caudal ventral respiratory group (VRG), nucleus tractus solitarius (NTS), and n. raphe obscurus. Efferent phrenic nerve activity was recorded. Spike trains of 889 neurons were analyzed with cycle-triggered histograms and tested for respiratory-modulated firing rates. Responses to stimulus protocols were assessed with peristimulus time and cumulative sum histograms. Cross-correlation analysis was used to test for nonrandom temporal relationships between spike trains. Spike-triggered averages of efferent phrenic activity and antidromic stimulation methods provided evidence for functional associations of bulbar neurons with phrenic motoneurons. Spike train cross-correlograms were calculated for 6,471 pairs of neurons. Significant correlogram features were detected for 425 pairs, including 189 primary central peaks or troughs, 156 offset peaks or troughs, and 80 pairs with multiple peaks and troughs. The results provide evidence that correlational medullary assemblies include neurons with overlapping memberships in groups responsive to different sets of sensory modalities. The data suggest and support several hypotheses concerning cooperative relationships that modulate the respiratory motor pattern. 1) Neurons responsive to a single tested modality promote or limit changes in firing rate of multimodal target neurons. 2) Multimodal neurons contribute to changes in firing rate of neurons responsive to a single tested modality. 3) Multimodal neurons may promote responses during stimulation of one modality and “limit” changes in firing rates during stimulation of another sensory modality. 4) Caudal VRG inspiratory neurons have inhibitory connections that provide negative feedback regulation of inspiratory drive and phase duration.

scholarly journals Synaesthesia in Autism

2016 ◽  
Vol 14 (3) ◽  
pp. 21-31 ◽  
Author(s):  
O.B. Bogdashina
Keyword(s):  
Autism Spectrum Disorders ◽  
Sensory Modality ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Sensory Modalities ◽  
Spectrum Disorders ◽  
Stimulation Of

Synaesthesia — a phenomenon of perception, when stimulation of one sensory modality triggers a perception in one or more other sensory modalities. Synaesthesia is not uniform and can manifest itself in different ways. As the sensations and their interpretation vary in different periods of time, it makes it hard to study this phenom¬enon. The article presents the classification of different forms of synaesthesia, including sensory and cognitive; and bimodal and multimodal synaesthesia. Some synaesthetes have several forms and variants of synaesthesia, while others – just one form of it. Although synaesthesia is not specific to autism spectrum disorders, it is quite common among autistic individuals. The article deals with the most common forms of synaesthesia in autism, advantages and problems of synesthetic perception in children with autism spectrum disorders, and provides some advice to parents how to recognise synaesthesia in children with autism.

scholarly journals Left Inferior Frontal Gyrus Integrates Multisensory Information in Category Learning

2020 ◽  
Vol 30 (8) ◽  
pp. 4410-4423
Author(s):  
You Li ◽  
Carol Seger ◽  
Qi Chen ◽  
Lei Mo
Keyword(s):  
Category Learning ◽  
Information Integration ◽  
Multisensory Processing ◽  
Inferior Frontal Gyrus ◽  
Sensory Modality ◽  
Precentral Gyrus ◽  
General Network ◽  
Multisensory Information ◽  
First Time

Abstract Humans are able to categorize things they encounter in the world (e.g., a cat) by integrating multisensory information from the auditory and visual modalities with ease and speed. However, how the brain learns multisensory categories remains elusive. The present study used functional magnetic resonance imaging to investigate, for the first time, the neural mechanisms underpinning multisensory information-integration (II) category learning. A sensory-modality-general network, including the left insula, right inferior frontal gyrus (IFG), supplementary motor area, left precentral gyrus, bilateral parietal cortex, and right caudate and globus pallidus, was recruited for II categorization, regardless of whether the information came from a single modality or from multiple modalities. Putamen activity was higher in correct categorization than incorrect categorization. Critically, the left IFG and left body and tail of the caudate were activated in multisensory II categorization but not in unisensory II categorization, which suggests this network plays a specific role in integrating multisensory information during category learning. The present results extend our understanding of the role of the left IFG in multisensory processing from the linguistic domain to a broader role in audiovisual learning.

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