Behavioural correlate of choice confidence in a discrete trial paradigm

How animals make choices in a changing and often uncertain environment is a central theme in the behavioural sciences. There is a substantial literature on how animals make choices in various experimental paradigms but less is known about the way they assess a choice after it has been made in terms of the expected outcome. Here, we used a discrete trial paradigm to characterise how the reward history shaped the behaviour on a trial by trial basis. Rats initiated each trial which consisted of a choice between two drinking spouts that differed in their probability of delivering a sucrose solution. Critically, sucrose was delivered after a delay from the first lick at the spouts--this allowed us to characterise the behavioural profile during the window between the time of choice and its outcome. Rats' behaviour converged to optimum choice, both during the acquisition phase and after the reversal of contingencies. We monitored the post-choice behaviour at a temporal precision of 1 millisecond; lick-response profiles revealed that rats spent more time at the spout with the higher reward probability and exhibited a sparser lick pattern. This was the case when we exclusively examined the unrewarded trials, where the outcome was identical. The differential licking profiles preceded the differential choice ratios and could thus predict the changes in choice behaviour.This research was supported by the Australian Research Council Discovery Project Grant DP0987133 to EA

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 um 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.This work was supported by the Australian Research Council Discovery Project DP0987133 and the Australian National Health and Medical Research Council Project Grant 1028670

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

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

Evaluation of the frequency of the IL-28 polymorphism (rs8099917) in patients with chronic hepatitis C using zip nucleic acid probes, Kerman, Southeast of Iran

Polymorphisms in the region of the interleukin IL-28 gene on chromosome 19 have been related with clearance of hepatitis C virus (HCV), a major human pathogen responsible for chronic hepatitis, cirrhosis and hepatocellular carcinoma. About 3 of the world's population is infected with HCV. The long-term response to therapy is influenced by many host and viral factors, and recent evidence has indicated that some host genetic polymorphisms related to IL-28 are the most powerful predictors of virological response in patients with HCV. This study assessed frequency of the IL-28 polymorphism (rs8099917) in 50 patients (39 men and 11 women ) with chronic hepatitis C using ZNA probe real time PCR new method . All patients were tested for genotype of HCV and the HCV viral load. In parallel, the levels of SGOT, SGPT and ALK enzymes were assessed. Treatment using Peg-interferon alpha with ribavirin was conducted for patients and subsequently samples were collected to detect any change in viral load or liver enzyme rates. The overall frequency of the TT allele is 74, TG allele 20 and GG allele 6 and the percent of patients who had T allele was 84. Clear reduction in viral load and liver enzymes was reported in patients with the T allele. Especially for genotype 1 which is relatively resistant to treatment, these alleles may have a role in this decline. In conclusion, we showed that IL-28 polymorphism rs8099917 strongly predicts virological response in HCV infection and that real-time PCR with Zip nucleic acid probes is a sensitive, specific and rapid detection method for detection of SNPs which will be essential for monitoring patients undergoing antiviral therapy

Integration of visual and whisker signals in rat superior colliculus

Multisensory integration is a process by which signals from different sensory modalities are combined to facilitate detection and localization of external events. One substrate for multisensory integration is the midbrain superior colliculus (SC) which plays an important role in orienting behavior. In rodent SC, visual and somatosensory (whisker) representations are in approximate registration, but whether and how these signals interact is unclear. We measured spiking activity in SC of anesthetized hooded rats, during presentation of visual- and whisker stimuli that were tested simultaneously or in isolation. Visual responses were found in all layers, but were primarily located in superficial layers. Whisker responsive sites were primarily found in intermediate layers. In single- and multi-unit recording sites, spiking activity was usually only sensitive to one modality, when stimuli were presented in isolation. By contrast, we observed robust and primarily suppressive interactions when stimuli were presented simultaneously to both modalities. We conclude that while visual and whisker representations in SC of rat are partially overlapping, there is limited excitatory convergence onto individual sites. Multimodal integration may instead rely on suppressive interactions between modalities

WNT5A-ROR2 is induced by inflammatory mediators and is involved in the migration of human ovarian cancer cell line SKOV-3

Background: Wnt5A, which is a member of the non-transforming Wnt protein family, is implicated in inflammatory processes. It is also highly expressed by ovarian cancer cells. ROR2, which is a member of the Ror-family of receptor tyrosine kinases, acts as a receptor or co-receptor for Wnt5A. The Wnt5A-ROR2 signaling pathway plays essential roles in the migration and invasion of several types of tumor cell and influences their cell polarity. We investigated the modulation of Wnt5A-ROR2 by inflammatory mediators and its involvement in the migration of the human ovarian cancer cell line SKOV-3. Methods: SKOV-3 cells were treated with LPS (lipopolysaccharide), LTA (lipoteichoic acid) and recombinant human IL-6 alone or in combination with STAT3 inhibitor (S1155S31-201) or NF-kB inhibitor (BAY11-7082) for 4, 8, 12, 24 and 48 h. The Wnt5A and ROR2 expression levels were determined at the gene and protein levels. Cells were transfected with specific siRNA against Wnt5A in the absence or presence of human anti-ROR2 antibody and cell migration was assessed using transwells. Results: There was a strong downregulation of Wnt5A expression in the presence of STAT3 or NF-kB inhibitors. Cell stimulation with LTA or IL-6 for 8 h led to significantly increased levels of Wnt5A (5- and 3-fold higher, respectively). LPS, LTA or IL-6 treatment significantly increased ROR2 expression (2-fold after 48 h). LPS- or LTA-induced Wnt5A or ROR2 expression was abrogated in the presence of STAT3 inhibitor (p < 0.001). IL-6-induced Wnt5A expression was abrogated by both STAT3 and NF-kB inhibitors (p < 0.001). Although not significant, IL-6-induced ROR2 expression showed a modest decrease when STAT3 inhibitor was used. Moreover, cell migration was decreased by 80 in siRNA Wnt5A-transfected cells in the presence of anti-human ROR2 antibody (p < 0.001). Conclusions: This study revealed for the first time that inflammatory mediators modulate Wnt5A and ROR2 through NF-kB and STAT3 transcription factors and this may play a role in ovarian cancer cell migration. The results described here provide new insight into the role of the Wnt5A-ROR2 complex in ovarian cancer progression in relation to inflammation. � 2016 The Author(s)

Synthesis and Optimization of Reversible Circuits - A Survey

Reversible logic circuits have been historically motivated by theoretical research in low-power electronics as well as practical improvement of bit-manipulation transforms in cryptography and computer graphics. Recently, reversible circuits have attracted interest as components of quantum algorithms, as well as in photonic and nano-computing technologies where some switching devices offer no signal gain. Research in generating reversible logic distinguishes between circuit synthesis, post-synthesis optimization, and technology mapping. In this survey, we review algorithmic paradigms --- search-based, cycle-based, transformation-based, and BDD-based --- as well as specific algorithms for reversible synthesis, both exact and heuristic. We conclude the survey by outlining key open challenges in synthesis of reversible and quantum logic, as well as most common misconceptions.Comment: 34 pages, 15 figures, 2 table

Shifts in Coding Properties and Maintenance of Information Transmission during Adaptation in Barrel Cortex

Neuronal responses to ongoing stimulation in many systems change over time, or “adapt.” Despite the ubiquity of adaptation, its effects on the stimulus information carried by neurons are often unknown. Here we examine how adaptation affects sensory coding in barrel cortex. We used spike-triggered covariance analysis of single-neuron responses to continuous, rapidly varying vibrissa motion stimuli, recorded in anesthetized rats. Changes in stimulus statistics induced spike rate adaptation over hundreds of milliseconds. Vibrissa motion encoding changed with adaptation as follows. In every neuron that showed rate adaptation, the input–output tuning function scaled with the changes in stimulus distribution, allowing the neurons to maintain the quantity of information conveyed about stimulus features. A single neuron that did not show rate adaptation also lacked input–output rescaling and did not maintain information across changes in stimulus statistics. Therefore, in barrel cortex, rate adaptation occurs on a slow timescale relative to the features driving spikes and is associated with gain rescaling matched to the stimulus distribution. Our results suggest that adaptation enhances tactile representations in primary somatosensory cortex, where they could directly influence perceptual decisions

Electrophysiological characterization of texture information slip-resistance dependent in the rat vibrissal nerve

<p>Abstract</p> <p>Background</p> <p>Studies in tactile discrimination agree that rats are able to learn a rough-smooth discrimination task by actively touching (whisking) objects with their vibrissae. In particular, we focus on recent evidence of how neurons at different levels of the sensory pathway carry information about tactile stimuli. Here, we analyzed the multifiber afferent discharge of one vibrissal nerve during active whisking. Vibrissae movements were induced by electrical stimulation of motor branches of the facial nerve. We used sandpapers of different grain size as roughness discrimination surfaces and we also consider the change of vibrissal slip-resistance as a way to improve tactile information acquisition. The amplitude of afferent activity was analyzed according to its Root Mean Square value (RMS). The comparisons among experimental situation were quantified by using the information theory.</p> <p>Results</p> <p>We found that the change of the vibrissal slip-resistance is a way to improve the roughness discrimination of surfaces. As roughness increased, the RMS values also increased in almost all cases. In addition, we observed a better discrimination performance in the retraction phase (maximum amount of information).</p> <p>Conclusions</p> <p>The evidence of amplitude changes due to roughness surfaces and slip-resistance levels allows to speculate that texture information is slip-resistance dependent at peripheral level.</p