Neurons and astrocytes interaction in neuronal network: A game-theoretic approach.

A neuron is the fundamental unit of the nervous system and the brain, crucial for transducing information in form of trains of electrical pulses known as action potentials. The connection between neurons is through synapses, enabling communication between neurons. This communication link is one of the key elements in processing of information from a neuron to another neuron. The strength of the synapses may vary over time, a phenomenon known as synaptic plasticity. This is the process by which it is believed memory and learning is governed. Recent studies revealed environmental factors affect the strength of synapses, and the way neurons communicate to each other. This poses the question as to what extent the pre- and post- synaptic neurons sense the environmental changes, and in turn adjust their synaptic link. Here, we model the behavior of an interconnected neuronal network in various environmental conditions as a multi-agent system in a game theoretic framework. We focus on a CA1 lattice subfield as an example plastic neuronal network. Our analysis revealed the neuronal network converges to different equilibria depending on the environmental changes. The model well-predicts the behavior of the network compared to a well-known theoretical model of individual neurons.

Population decoding in rat barrel cortex: optimizing the linear readout of correlated population responses.

Sensory information is encoded in the response of neuronal populations. How might this information be decoded by downstream neurons? Here we analyzed the responses of simultaneously recorded barrel cortex neurons to sinusoidal vibrations of varying amplitudes preceded by three adapting stimuli of 0, 6 and 12 µm in amplitude. Using the framework of signal detection theory, we quantified the performance of a linear decoder which sums the responses of neurons after applying an optimum set of weights. Optimum weights were found by the analytical solution that maximized the average signal-to-noise ratio based on Fisher linear discriminant analysis. This provided a biologically plausible decoder that took into account the neuronal variability, covariability, and signal correlations. The optimal decoder achieved consistent improvement in discrimination performance over simple pooling. Decorrelating neuronal responses by trial shuffling revealed that, unlike pooling, the performance of the optimal decoder was minimally affected by noise correlation. In the non-adapted state, noise correlation enhanced the performance of the optimal decoder for some populations. Under adaptation, however, noise correlation always degraded the performance of the optimal decoder. Nonetheless, sensory adaptation improved the performance of the optimal decoder mainly by increasing signal correlation more than noise correlation. Adaptation induced little systematic change in the relative direction of signal and noise. Thus, a decoder which was optimized under the non-adapted state generalized well across states of adaptation.

Behavioral study of whisker-mediated vibration sensation in rats.

Rats use their vibrissal sensory system to collect information about the nearby environment. They can accurately and rapidly identify object location, shape, and surface texture. Which features of whisker motion does the sensory system extract to construct sensations? We addressed this question by training rats to make discriminations between sinusoidal vibrations simultaneously presented to the left and right whiskers. One set of rats learned to reliably identify which of two vibrations had higher frequency (f(1) vs. f(2)) when amplitudes were equal. Another set of rats learned to reliably identify which of two vibrations had higher amplitude (A(1) vs. A(2)) when frequencies were equal. Although these results indicate that both elemental features contribute to the rats' sensation, a further test found that the capacity to discriminate A and f was reduced to chance when the difference in one feature was counterbalanced by the difference in the other feature: Rats could not discriminate amplitude or frequency whenever A(1)f(1) = A(2)f(2). Thus, vibrations were sensed as the product Af rather than as separable elemental features, A and f. The product Af is proportional to a physical entity, the mean speed. Analysis of performance revealed that rats extracted more information about differences in Af than predicted by the sum of the information in elemental differences. These behavioral experiments support the predictions of earlier physiological studies by demonstrating that rats are "blind" to the elemental features present in a sinusoidal whisker vibration; instead, they perceive a composite feature, the speed of whisker motion.

Informational basis of sensory adaptation: entropy and single-spike efficiency in rat barrel cortex.

We showed recently that exposure to whisker vibrations enhances coding efficiency in rat barrel cortex despite increasing correlations in variability (Adibi et al., 2013). Here, to understand how adaptation achieves this improvement in sensory representation, we decomposed the stimulus information carried in neuronal population activity into its fundamental components in the framework of information theory. In the context of sensory coding, these components are the entropy of the responses across the entire stimulus set (response entropy) and the entropy of the responses conditional on the stimulus (conditional response entropy). We found that adaptation decreased response entropy and conditional response entropy at both the level of single neurons and the pooled activity of neuronal populations. However, the net effect of adaptation was to increase the mutual information because the drop in the conditional entropy outweighed the drop in the response entropy. The information transmitted by a single spike also increased under adaptation. As population size increased, the information content of individual spikes declined but the relative improvement attributable to adaptation was maintained.

Adaptation improves neural coding efficiency despite increasing correlations in variability.

Exposure of cortical cells to sustained sensory stimuli results in changes in the neuronal response function. This phenomenon, known as adaptation, is a common feature across sensory modalities. Here, we quantified the functional effect of adaptation on the ensemble activity of cortical neurons in the rat whisker-barrel system. A multishank array of electrodes was used to allow simultaneous sampling of neuronal activity. We characterized the response of neurons to sinusoidal whisker vibrations of varying amplitude in three states of adaptation. The adaptors produced a systematic rightward shift in the neuronal response function. Consistently, mutual information revealed that peak discrimination performance was not aligned to the adaptor but to test amplitudes 3-9 µm higher. Stimulus presentation reduced single neuron trial-to-trial response variability (captured by Fano factor) and correlations in the population response variability (noise correlation). We found that these two types of variability were inversely proportional to the average firing rate regardless of the adaptation state. Adaptation transferred the neuronal operating regime to lower rates with higher Fano factor and noise correlations. Noise correlations were positive and in the direction of signal, and thus detrimental to coding efficiency. Interestingly, across all population sizes, the net effect of adaptation was to increase the total information despite increasing the noise correlation between neurons.

A comparison of neuronal and behavioral detection and discrimination performances in rat whisker system.

We used the rat whisker touch as a model system to investigate the correlation between the response function of cortical neurons and the behavior of rats in a sensory detection versus discrimination task. The rat whisker-barrel system is structurally well characterized and represents one of the main channels through which rodents collect information about the environment. In experiment 1, we recorded neuronal activity (n = 235) in the whisker area of the rat somatosensory cortex in anesthetized rats while applying vibrotactile stimuli of varying amplitudes to the whiskers. Neurons showed a characteristic sigmoidal input-output function, with an accelerating nonlinearity at low stimulus amplitudes and a compressive nonlinearity at high stimulus amplitudes. We further quantified the performance of individual neurons for stimulus detection and for discrimination across different stimulus pairs with identical amplitude differences. For near-threshold stimuli, the neuronal discrimination performance surpassed the detection performance despite the fact that detection and discrimination represented identical amplitude differences. This is consistent with the accelerating nonlinearity observed at low stimulus intensities. In the second stage of the experiment, four rats were trained to select the higher-amplitude stimulus between two vibrations applied to their whiskers. Similar to neuronal results, the rats' performance was better for the discrimination task compared with the detection task. The behavioral performance followed the same trend as that of the population of individual neurons. Both behavioral and neuronal data are consistent with the "pedestal effect" previously reported in human psychophysics.

Sensory Adaptation in the Whisker-Mediated Tactile System: Physiology, Theory, and Function.

In the natural environment, organisms are constantly exposed to a continuous stream of sensory input. The dynamics of sensory input changes with organism's behaviour and environmental context. The contextual variations may induce >100-fold change in the parameters of the stimulation that an animal experiences. Thus, it is vital for the organism to adapt to the new diet of stimulation. The response properties of neurons, in turn, dynamically adjust to the prevailing properties of sensory stimulation, a process known as "neuronal adaptation." Neuronal adaptation is a ubiquitous phenomenon across all sensory modalities and occurs at different stages of processing from periphery to cortex. In spite of the wealth of research on contextual modulation and neuronal adaptation in visual and auditory systems, the neuronal and computational basis of sensory adaptation in somatosensory system is less understood. Here, we summarise the recent finding and views about the neuronal adaptation in the rodent whisker-mediated tactile system and further summarise the functional effect of neuronal adaptation on the response dynamics and encoding efficiency of neurons at single cell and population levels along the whisker-mediated touch system in rodents. Based on direct and indirect pieces of evidence presented here, we suggest sensory adaptation provides context-dependent functional mechanisms for noise reduction in sensory processing, salience processing and deviant stimulus detection, shift between integration and coincidence detection, band-pass frequency filtering, adjusting neuronal receptive fields, enhancing neural coding and improving discriminability around adapting stimuli, energy conservation, and disambiguating encoding of principal features of tactile stimuli.

Whisker-Mediated Touch System in Rodents: From Neuron to Behavior.

A key question in systems neuroscience is to identify how sensory stimuli are represented in neuronal activity, and how the activity of sensory neurons in turn is "read out" by downstream neurons and give rise to behavior. The choice of a proper model system to address these questions, is therefore a crucial step. Over the past decade, the increasingly powerful array of experimental approaches that has become available in non-primate models (e.g., optogenetics and two-photon imaging) has spurred a renewed interest for the use of rodent models in systems neuroscience research. Here, I introduce the rodent whisker-mediated touch system as a structurally well-established and well-organized model system which, despite its simplicity, gives rise to complex behaviors. This system serves as a behaviorally efficient model system; known as nocturnal animals, along with their olfaction, rodents rely on their whisker-mediated touch system to collect information about their surrounding environment. Moreover, this system represents a well-studied circuitry with a somatotopic organization. At every stage of processing, one can identify anatomical and functional topographic maps of whiskers; "barrelettes" in the brainstem nuclei, "barreloids" in the sensory thalamus, and "barrels" in the cortex. This article provides a brief review on the basic anatomy and function of the whisker system in rodents.

Publisher Correction: Response dynamics of rat barrel cortex neurons to repeated sensory stimulation.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Response dynamics of rat barrel cortex neurons to repeated sensory stimulation.

Neuronal adaptation is a common feature observed at various stages of sensory processing. Here, we quantified the time course of adaptation in rat somatosensory cortex. Under urethane anesthesia, we juxta-cellularly recorded single neurons (n = 147) while applying a series of whisker deflections at various frequencies (2-32 Hz). For ~90% of neurons, the response per unit of time decreased with frequency. The degree of adaptation increased along the train of deflections and was strongest at the highest frequency. However, a subset of neurons showed facilitation producing higher responses to subsequent deflections. The response latency to consecutive deflections increased both for neurons that exhibited adaptation and for those that exhibited response facilitation. Histological reconstruction of neurons (n = 45) did not reveal a systematic relationship between adaptation profiles and cell types. In addition to the periodic stimuli, we applied a temporally irregular train of deflections with a mean frequency of 8 Hz. For 70% of neurons, the response to the irregular stimulus was greater than that of the 8 Hz regular. This increased response to irregular stimulation was positively correlated with the degree of adaptation. Altogether, our findings demonstrate high levels of diversity among cortical neurons, with a proportion of neurons showing facilitation at specific temporal intervals.

Dynamics of Population Activity in Rat Sensory Cortex: Network Correlations Predict Anatomical Arrangement and Information Content.

To study the spatiotemporal dynamics of neural activity in a cortical population, we implanted a 10 × 10 microelectrode array in the vibrissal cortex of urethane-anesthetized rats. We recorded spontaneous neuronal activity as well as activity evoked in response to sustained and brief sensory stimulation. To quantify the temporal dynamics of activity, we computed the probability distribution function (PDF) of spiking on one electrode given the observation of a spike on another. The spike-triggered PDFs quantified the strength, temporal delay, and temporal precision of correlated activity across electrodes. Nearby cells showed higher levels of correlation at short delays, whereas distant cells showed lower levels of correlation, which tended to occur at longer delays. We found that functional space built based on the strength of pairwise correlations predicted the anatomical arrangement of electrodes. Moreover, the correlation profile of electrode pairs during spontaneous activity predicted the "signal" and "noise" correlations during sensory stimulation. Finally, mutual information analyses revealed that neurons with stronger correlations to the network during spontaneous activity, conveyed higher information about the sensory stimuli in their evoked response. Given the 400-µm-distance between adjacent electrodes, our functional quantifications unravel the spatiotemporal dynamics of activity among nearby and distant cortical columns.

Correlation between Cortical State and Locus Coeruleus Activity: Implications for Sensory Coding in Rat Barrel Cortex.

Cortical state modulates the background activity of cortical neurons, and their evoked response to sensory stimulation. Multiple mechanisms are involved in switching between cortical states including various neuromodulatory systems. Locus Coeruleus (LC) is one of the major neuromodulatory nuclei in the brainstem with widespread projections throughout the brain and modulates the activity of cells and networks. Here, we quantified the link between the LC spontaneous activity, cortical state and sensory processing in the rat vibrissal somatosensory "barrel" cortex (BC). We simultaneously recorded unit activity from LC and BC along with prefrontal electroencephalogram (EEG) while presenting brief whisker deflections under urethane anesthesia. The ratio of low to high frequency components of EEG (referred to as the L/H ratio) was employed to identify cortical state. We found that the spontaneous activity of LC units exhibited a negative correlation with the L/H ratio. Cross-correlation analysis revealed that changes in LC firing preceded changes in the cortical state: the correlation of the LC firing profile with the L/H ratio was maximal at an average lag of -1.2 s. We further quantified BC neuronal responses to whisker stimulation during the synchronized and desynchronized states. In the desynchronized state, BC neurons showed lower stimulus detection threshold, higher response fidelity, and shorter response latency. The most prominent change was observed in the late phase of BC evoked activity (100-400 ms post stimulus onset): almost every BC unit exhibited a greater late response during the desynchronized state. Categorization of the BC evoked responses based on LC activity (into high and low LC discharge rates) resulted in highly similar response profiles compared to categorization based on the cortical state (low and high L/H ratios). These findings provide evidence for the involvement of the LC neuromodulatory system in desynchronization of cortical state and the consequent enhancement of sensory coding efficiency.

Configural and analytical processing of familiar and unfamiliar objects.

Configural processing could develop for non-face visual objects as one becomes familiar with those objects through repeated exposure. To explore the role of familiarity in object recognition, we studied the effect of adaptation to a visual object (adapting stimulus) on the identification performance of other objects (test stimulus) while adapting and test stimuli were exactly the same, shared parts or were completely different. We used a subset of English alphabets (p, q, d and b) as familiar objects and an unfamiliar set of symbols constructed from same parts but with different configurations. Adaptation to a member of each set led to a lower identification performance for that object in a crowding paradigm. Adaptation to each member of the unfamiliar set resulted in decreased identification performance for the same object and those members of the set that shared parts with the adapting stimulus. But no such transfer of adaptation was observed for the familiar set. Our results support the notion that processing of object parts plays an important role in the recognition of unfamiliar objects while recognition of familiar objects is mainly based on configural processing mechanisms.

Sampling time and performance in rat whisker sensory system.

We designed a behavioural paradigm for vibro-tactile detection to characterise the sampling time and performance in the rat whisker sensory system. Rats initiated a trial by nose-poking into an aperture where their whiskers came into contact with two meshes. A continuous nose-poke for a random duration triggered stimulus presentation. Stimuli were a sequence of discrete Gaussian deflections of the mesh that increased in amplitude over time - across 5 conditions, time to maximum amplitude varied from 0.5 to 8 seconds. Rats indicated the detected stimulus by choosing between two reward spouts. Two rats completed more than 500 trials per condition. Rats' stimulus sampling duration increased and performance dropped with increasing task difficulty. For all conditions the median reaction time was longer for correct trials than incorrect trials. Higher rates of increment in stimulus amplitude resulted in faster rise in performance as a function of stimulus sampling duration. Rats' behaviour indicated a dynamic stimulus sampling whereby nose-poke was maintained until a stimulus was correctly identified or the rat experienced a false alarm. The perception was then manifested in behaviour after a motor delay. We thus modelled the results with 3 parameters: signal detection, false alarm, and motor delay. The model captured the main features of the data and produced parameter estimates that were biologically plausible and highly similar across the two rats.