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

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.

Deficient GABAergic Gliotransmission May Cause Broader Sensory Tuning in Schizophrenia

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.

A Hierarchical Dynamical Map as a Basic Frame for Cortical Mapping and Its Application to Priming

A hierarchical dynamical map is proposed as the basic framework for sensory cortical mapping. To show how the hierarchical dynamical map works in cognitive processes, we applied it to a typical cognitive task known as priming, in which cognitive performance is facilitated as a consequence of prior experience. Prior to the priming task, the network memorizes a sensory scene containing multiple objects presented simultaneously using a hierarchical dynamical map. Each object is composed of different sensory features. The hierarchical dynamical map presented here is formed by random itinerancy among limit-cycle attractors into which these objects are encoded. Each limit-cycle attractor contains multiple point attractors into which elemental features belonging to the same object are encoded. When a feature stimulus is presented as a priming cue, the network state is changed from the itinerant state to a limit-cycle attractor relevant to the priming cue. After a short priming period, the network state reverts to the itinerant state. Under application of the test cue, consisting of some feature belonging to the object relevant to the priming cue and fragments of features belonging to others, the network state is changed to a limit-cycle attractor and finally to a point attractor relevant to the target feature. This process is considered as the identification of the target. The model consistently reproduces various observed results for priming processes such as the difference in identification time between cross-modality and within-modality priming tasks, the effect of interval between priming cue and test cue on identification time, the effect of priming duration on the time, and the effect of repetition of the same priming task on neural activity.

Blocking of Occasion Setting in Feature-Positive Discriminations

In two experiments rats received feature-positive discrimination training in which brief conditioned stimuli (CSs) were paired with food during presentations of an extended feature stimulus, and non-reinforced in its absence. In Experiment 1 a novel feature was trained in compound with a second, pretrained feature. Acquisition of control over responding to the CS by the novel feature was blocked if the pretrained feature had also been trained in a feature-positive discrimination, compared to a group for whom the pretrained feature had been accompanied by uncorrelated presentations of CSs and food. Experiment 2 employed a within-subjects design. It demonstrated that the feature from a feature-positive discrimination with a particular CS, x, blocked acquisition of control by an added, novel feature over responding to x, compared to the control acquired by the same novel feature over a novel, CS y.