Ongoing Spontaneous Neuronal Activity Research Articles

Perceptual judgments via sensory-motor interaction assisted by cortical GABA.

Recurrent input to sensory cortex, via long-range reciprocal projections between motor and sensory cortices, is essential for accurate perceptual judgments. GABA levels in sensory cortices correlate with perceptual performance. We simulated a neuron-astrocyte network model to investigate how top-down, feedback signaling from a motor network (Nmot) to a sensory network (Nsen) affects perceptual judgments in association with ambient (extracellular) GABA levels. In the Nsen, astrocytic transporters modulated ambient GABA levels around pyramidal cells. A simple perceptual task was implemented: detection of a feature stimulus presented to the Nsen. The Nmot showed distinct perceptual behaviors: hit, fault, and miss. A hit is a correct response to the stimulus, a fault is a wrong response to the stimulus, and a miss is no response to the stimulus. In hits, the feedback signaling increased the gain of Nsen pyramidal cells and accelerated the reaction speed of Nmot pyramidal cells to the stimulus. Without feedback signaling, the Nsen but not Nmot responded to the stimulus, resulting in a miss. With too strong feedback signaling, the Nmot resulted in a fault, namely, stimulus-insensitive but not stimulus-sensitive pyramidal cells wrongly responded. Balancing the feedforward and feedback signaling formed a coherent, ongoing-spontaneous neuronal state, by which the highest hit rate was achieved. A transient reduction in local ambient GABA levels, triggered by the stimulus, contributed to accelerating the reaction speed under noisy environmental conditions. Adjusting the basal ambient GABA level ensured high hit rates. We suggest that motor cortex feedback may accelerate reaction speed to sensory stimulation by promoting coherency in ongoing-spontaneous neuronal activity between sensory and motor cortices, thereby achieving prompt perceptual judgments. Spatiotemporal modulation of ambient GABA levels, possibly by astrocytic transporters, assists in making reliable perceptual judgments.

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 GABAa 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.

Effects of Acoustic Stimuli on Neuronal Activity in the Auditory Cortex of the Rat

Spontaneous activity of cortical neurons exhibits alternative fluctuations of membrane potential consisting of phased depolarization called "up-state" and persistent hyperpolarization called "down-state" during slow wave sleep and anesthesia. Here, we examined the effects of sound stimuli (noise bursts) on neuronal activity by intracellular recording in vivo from the rat auditory cortex (AC). Noise bursts increased the average time in the up-state by 0.81+/-0.65 s (range, 0.27-1.74 s) related to a 10 s recording duration. The rise times of the spontaneous up-events averaged 69.41+/-18.04 ms (range, 40.10-119.21 ms), while those of the sound-evoked up-events were significantly shorter (p<0.001) averaging only 22.54+/-8.81 ms (range, 9.31-45.74 ms). Sound stimulation did not influence ongoing spontaneous up-events. Our data suggest that a sound stimulus does not interfere with ongoing spontaneous neuronal activity in auditory cortex but can evoke new depolarizations in addition to the spontaneous ones.

Insufficient augmentation of ambient GABA responsible for age-related cognitive deficit

Age-related degeneration of intracortical inhibition could underlie declines in cognitive function during senescence. Based on a hypothesis that a decrease in basal concentration of ambient (extrasynaptic) GABA with aging leads to depressing intracortical inhibition, we investigated how the basal concentration affects stimulus-evoked activity (as signal), ongoing-spontaneous activity (as noise) of neurons and their (signal-to-noise) ratio S/N. We simulated a neural network model equipped with a GABA transport system that regulates ambient GABA concentration in a neuronal activity-dependent manner. An increase in basal concentration augmented ambient GABA, increased GABA-mediated inhibitory current, and depressed ongoing-spontaneous activity while still keeping stimulus-evoked activity. This led to S/N improvement, for which it was necessary for the reversal potential of GABA transporter to be close to the resting potential of neurons. Above the resting potential, ongoing-spontaneous activity was predominantly enhanced due to excessive GABA-uptake from the extracellular space by transporters. Below the resting potential, stimulus-evoked activity was predominantly depressed, caused by excessive GABA-release. We suggest that the insufficient augmentation of ambient GABA due to a decrease in its basal concentration may be one of the possible causes of cognitive deficit with aging, increasing ongoing-spontaneous neuronal activity as noise. GABA transporter may contribute to improving S/N, provided that its reversal potential is close to the resting potential.

Local intracortical circuitry not only for feature binding but also for rapid neuronal responses

Neurons of primary sensory cortices are known to have specific responsiveness to elemental features. To express more complex sensory attributes that are embedded in objects or events, the brain must integrate them. This is referred to as feature binding and is reflected in correlated neuronal activity. We investigated how local intracortical circuitry modulates ongoing-spontaneous neuronal activity, which would have a great impact on the processing of subsequent combinatorial input, namely, on the correlating (binding) of relevant features. We simulated a functional, minimal neural network model of primary visual cortex, in which lateral excitatory connections were made in a diffusive manner between cell assemblies that function as orientation columns. A pair of bars oriented at specific angles, expressing a visual corner, was applied to the network. The local intracortical circuitry contributed not only to inducing correlated neuronal activation and thus to binding the paired features but also to making membrane potentials oscillate at firing-subthreshold during an ongoing-spontaneous time period. This led to accelerating the reaction speed of principal cells to the input. If the lateral excitatory connections were selectively (instead of "diffusively") made, hyperpolarization in ongoing membrane potential occurred and thus the reaction speed was decelerated. We suggest that the local intracortical circuitry with diffusive connections between cell assemblies might endow the network with an ongoing subthreshold neuronal state, by which it can send the information about combinations of elemental features rapidly to higher cortical stages for their full and precise analyses.

GABA Transporter Preserving Ongoing Spontaneous Neuronal Activity at Firing Subthreshold

There has been compelling evidence that the GABA transporter is crucial not only for removing gamma-aminobutyric acid (GABA) from but also releasing it into extracellular space, thereby clamping ambient GABA (GABA in extracellular space) at a certain level. The ambient GABA is known to activate extrasynaptic GABA receptors and provide tonic inhibitory current into neurons. We investigated how the transporter regulates the level of ambient GABA, mediates tonic neuronal inhibition, and influences ongoing spontaneous neuronal activity. A cortical neural network model is proposed in which GABA transporters on lateral (L) and feedback (F) inhibitory (GABAergic) interneurons are functionally made. Principal (P) cell assemblies participate in expressing information about elemental sensory features. At membrane potentials below the reversal potential, there is net influx of GABA, whereas at membrane potentials above the reversal potential, there is net efflux of GABA. Through this transport mechanism, ambient GABA concentration is kept within a submicromolar range during an ongoing spontaneous neuronal activity time period. Here we show that the GABA transporter on L cells regulates the overall level of ambient GABA across cell assemblies, and that on F cells it does so within individual cell assemblies. This combinatorial regulation of ambient GABA allows P cells to oscillate near firing threshold during the ongoing time period, thereby reducing their reaction time to externally applied stimuli. We suggest that the GABA transporter, with its forward and reverse transport mechanism, could regulate the ambient GABA. This transporter-mediated ambient GABA regulation may contribute to establishing an ongoing subthreshold neuronal state by which the network can respond rapidly to subsequent sensory input.

Coherent ongoing subthreshold state of a cortical neural network regulated by slow- and fast-spiking interneurons

Although details of cortical interneurons in anatomy and physiology have been well understood, little is known about how they contribute to ongoing spontaneous neuronal activity that could have a great impact on subsequent neuronal information processing. Simulating a cortical neural network model of an early sensory area, we investigated whether and how two distinct types of inhibitory interneurons, or fast-spiking interneurons with narrow axonal arbors and slow-spiking interneurons with wide axonal arbors, have a spatiotemporal influence on the ongoing activity of principal cells and subsequent cognitive information processing. In the model, dynamic cell assemblies, or population activation of principal cells, expressed information about specific sensory features. Within cell assemblies, fast-spiking interneurons give a feedback inhibitory effect on principal cells. Between cell assemblies, slow-spiking interneurons give a lateral inhibitory effect on principal cells. Here, we show that these interneurons keep the network at a subthreshold level for action potential generation under the ongoing state, by which the reaction time of principal cells to sensory stimulation could be accelerated. We suggest that the best timing of inhibition mediated by fast-spiking interneurons and slow-spiking interneurons allows the network to remain near threshold for rapid responses to input.

Nav 1.8-Null Mice Show Stimulus-Dependent Deficits in Spinal Neuronal Activity

BackgroundThe voltage gated sodium channel Nav 1.8 has a highly restricted expression pattern to predominantly nociceptive peripheral sensory neurones. Behaviourally Nav 1.8-null mice show an increased acute pain threshold to noxious mechanical pressure and also deficits in inflammatory and visceral, but not neuropathic pain. Here we have made in vivo electrophysiology recordings of dorsal horn neurones in intact anaesthetised Nav 1.8-null mice, in response to a wide range of stimuli to further the understanding of the functional roles of Nav 1.8 in pain transmission from the periphery to the spinal cord.ResultsNav 1.8-null mice showed marked deficits in the coding by dorsal horn neurones to mechanical, but not thermal, -evoked responses over the non-noxious and noxious range compared to littermate controls. Additionally, responses evoked to other stimulus modalities were also significantly reduced in Nav 1.8-null mice where the reduction observed to pinch > brush. The occurrence of ongoing spontaneous neuronal activity was significantly less in mice lacking Nav 1.8 compared to control. No difference was observed between groups in the evoked activity to electrical activity of the peripheral receptive field.ConclusionThis study demonstrates that deletion of the sodium channel Nav 1.8 results in stimulus-dependent deficits in the dorsal horn neuronal coding to mechanical, but not thermal stimuli applied to the neuronal peripheral receptive field. This implies that Nav 1.8 is either responsible for, or associated with proteins involved in mechanosensation.