Detection of subthreshold pulses in neurons with channel noise

Neurons are subject to various kinds of noise. In addition to synaptic noise, the stochastic opening and closing of ion channels represents an intrinsic source of noise that affects the signal processing properties of the neuron. In this paper, we studied the response of a stochastic Hodgkin-Huxley neuron to transient input subthreshold pulses. It was found that the average response time decreases but variance increases as the amplitude of channel noise increases. In the case of single pulse detection, we show that channel noise enables one neuron to detect the subthreshold signals and an optimal membrane area (or channel noise intensity) exists for a single neuron to achieve optimal performance. However, the detection ability of a single neuron is limited by large errors. Here, we test a simple neuronal network that can enhance the pulse detecting abilities of neurons and find dozens of neurons can perfectly detect subthreshold pulses. The phenomenon of intrinsic stochastic resonance is also found both at the level of single neurons and at the level of networks. At the network level, the detection ability of networks can be optimized for the number of neurons comprising the network.Comment: 14 pages, 9 figure

Long-range electronic reconstruction to a dxz,yzd_{xz,yz}-dominated Fermi surface below the LaAlO3_3/SrTiO3_3 interface

Low dimensionality, broken symmetry and easily-modulated carrier concentrations provoke novel electronic phase emergence at oxide interfaces. However, the spatial extent of such reconstructions - i.e. the interfacial "depth" - remains unclear. Examining LaAlO$_3$/SrTiO$_3$ heterostructures at previously unexplored carrier densities $n_{2D}\geq6.9\times10^{14}$ cm$^{-2}$, we observe a Shubnikov-de Haas effect for small in-plane fields, characteristic of an anisotropic 3D Fermi surface with preferential $d_{xz,yz}$ orbital occupancy extending over at least 100~nm perpendicular to the interface. Quantum oscillations from the 3D Fermi surface of bulk doped SrTiO$_3$ emerge simultaneously at higher $n_{2D}$. We distinguish three areas in doped perovskite heterostructures: narrow ($<20$ nm) 2D interfaces housing superconductivity and/or other emergent phases, electronically isotropic regions far ($>120$ nm) from the interface and new intermediate zones where interfacial proximity renormalises the electronic structure relative to the bulk.Comment: Supplementary material available at Scientific Reports websit

The distribution and movement patterns of four woodland caribou herds in Quebec and Labrador

Recent studies of woodland caribou (Rangifer tarandus caribou) in northern Quebec and central Labrador have demonstrated similar patterns of seasonal movements and distribution among four herds. Aerial surveys and radio-telemetry indicated that animals occupied forest-wetland habitat at densities of 0.03 caribou km2, or lower, for most of the year. Although females were widely dispersed at calving individuals demonstrated fidelity toward specific calving locations, in successive years. Caribou did not form large post-calving aggregations. Movement was greatest in the spring, prior to calving, and in the fall, during or immediately after rutting. Caribou were generally sedentary during summer and winter, although some moved relatively long distances to late-winter range. Although the herds occupy continuous range across Quebec and Labrador, our data indicate that the herds are largely discreete and should be managed individually

ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory neurons

BACKGROUND: ASIC3, the most sensitive of the acid-sensing ion channels, depolarizes certain rat sensory neurons when lactic acid appears in the extracellular medium. Two functions have been proposed for it: 1) ASIC3 might trigger ischemic pain in heart and muscle; 2) it might contribute to some forms of touch mechanosensation. Here, we used immunocytochemistry, retrograde labelling, and electrophysiology to ask whether the distribution of ASIC3 in rat sensory neurons is consistent with either of these hypotheses. RESULTS: Less than half (40%) of dorsal root ganglion sensory neurons react with anti-ASIC3, and the population is heterogeneous. They vary widely in cell diameter and express different growth factor receptors: 68% express TrkA, the receptor for nerve growth factor, and 25% express TrkC, the NT3 growth factor receptor. Consistent with a role in muscle nociception, small (<25 μm) sensory neurons that innervate muscle are more likely to express ASIC3 than those that innervate skin (51% of small muscle afferents vs. 28% of small skin afferents). Over 80% of ASIC3+ muscle afferents co-express CGRP (a vasodilatory peptide). Remarkably few (9%) ASIC3+ cells express P2X3 receptors (an ATP-gated ion channel), whereas 31% express TRPV1 (the noxious heat and capsaicin-activated ion channel also known as VR1). ASIC3+/CGRP+ sensory nerve endings were observed on muscle arterioles, the blood vessels that control vascular resistance; like the cell bodies, the endings are P2X3- and can be TRPV1+. The TrkC+/ASIC3+ cell bodies are uniformly large, possibly consistent with non-nociceptive mechanosensation. They are not proprioceptors because they fail two other tests: ASIC3+ cells do not express parvalbumin and they are absent from the mesencephalic trigeminal nucleus. CONCLUSION: Our data indicates that: 1) ASIC3 is expressed in a restricted population of nociceptors and probably in some non-nociceptors; 2) co-expression of ASIC3 and CGRP, and the absence of P2X3, are distinguishing properties of a class of sensory neurons, some of which innervate blood vessels. We suggest that these latter afferents may be muscle metaboreceptors, neurons that sense the metabolic state of muscle and can trigger pain when there is insufficient oxygen

Subthreshold dynamics of the neural membrane potential driven by stochastic synaptic input

In the cerebral cortex, neurons are subject to a continuous bombardment of synaptic inputs originating from the network's background activity. This leads to ongoing, mostly subthreshold membrane dynamics that depends on the statistics of the background activity and of the synapses made on a neuron. Subthreshold membrane polarization is, in turn, a potent modulator of neural responses. The present paper analyzes the subthreshold dynamics of the neural membrane potential driven by synaptic inputs of stationary statistics. Synaptic inputs are considered in linear interaction. The analysis identifies regimes of input statistics which give rise to stationary, fluctuating, oscillatory, and unstable dynamics. In particular, I show that (i) mere noise inputs can drive the membrane potential into sustained, quasiperiodic oscillations (noise-driven oscillations), in the absence of a stimulus-derived, intraneural, or network pacemaker; (ii) adding hyperpolarizing to depolarizing synaptic input can increase neural activity (hyperpolarization-induced activity), in the absence of hyperpolarization-activated currents

Cannabis use and risk of schizophrenia: a Mendelian randomization study.

Cannabis use is observationally associated with an increased risk of schizophrenia, but whether the relationship is causal is not known. Using a genetic approach, we took 10 independent genetic variants previously identified to associate with cannabis use in 32 330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia. Genetic variants were employed as instruments to recapitulate a randomized controlled trial involving two groups (cannabis users vs nonusers) to estimate the causal effect of cannabis use on risk of schizophrenia in 34 241 cases and 45 604 controls from predominantly European descent. Genetically-derived estimates were compared with a meta-analysis of observational studies reporting ever use of cannabis and risk of schizophrenia or related disorders. Based on the genetic approach, use of cannabis was associated with increased risk of schizophrenia (odds ratio (OR) of schizophrenia for users vs nonusers of cannabis: 1.37; 95% confidence interval (CI), 1.09-1.67; P-value=0.007). The corresponding estimate from observational analysis was 1.43 (95% CI, 1.19-1.67; P-value for heterogeneity =0.76). The genetic markers did not show evidence of pleiotropic effects and accounting for tobacco exposure did not alter the association (OR of schizophrenia for users vs nonusers of cannabis, adjusted for ever vs never smoker: 1.41; 95% CI, 1.09-1.83). This adds to the substantial evidence base that has previously identified cannabis use to associate with increased risk of schizophrenia, by suggesting that the relationship is causal. Such robust evidence may inform public health messages about cannabis use, especially regarding its potential mental health consequences

Influence of history on saccade countermanding performance in humans and macaque monkeys

AbstractThe stop-signal or countermanding task probes the ability to control action by requiring subjects to withhold a planned movement in response to an infrequent stop signal which they do with variable success depending on the delay of the stop signal. We investigated whether performance of humans and macaque monkeys in a saccade countermanding task was influenced by stimulus and performance history. In spite of idiosyncrasies across subjects several trends were evident in both humans and monkeys. Response time decreased after successive trials with no stop signal. Response time increased after successive trials with a stop signal. However, post-error slowing was not observed. Increased response time was observed mainly or only after cancelled (signal inhibit) trials and not after noncancelled (signal respond) trials. These global trends were based on rapid adjustments of response time in response to momentary fluctuations in the fraction of stop signal trials. The effects of trial sequence on the probability of responding were weaker and more idiosyncratic across subjects when stop signal fraction was fixed. However, both response time and probability of responding were influenced strongly by variations in the fraction of stop signal trials. These results indicate that the race model of countermanding performance requires extension to account for these sequential dependencies and provide a basis for physiological studies of executive control of countermanding saccade performance

Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8 x 10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8 x 10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation

Standard and Embedded Solitons in Nematic Optical Fibers

A model for a non-Kerr cylindrical nematic fiber is presented. We use the multiple scales method to show the possibility of constructing different kinds of wavepackets of transverse magnetic (TM) modes propagating through the fiber. This procedure allows us to generate different hierarchies of nonlinear partial differential equations (PDEs) which describe the propagation of optical pulses along the fiber. We go beyond the usual weakly nonlinear limit of a Kerr medium and derive an extended Nonlinear Schrodinger equation (eNLS) with a third order derivative nonlinearity, governing the dynamics for the amplitude of the wavepacket. In this derivation the dispersion, self-focussing and diffraction in the nematic are taken into account. Although the resulting nonlinear $PDE$ may be reduced to the modified Korteweg de Vries equation (mKdV), it also has additional complex solutions which include two-parameter families of bright and dark complex solitons. We show analytically that under certain conditions, the bright solitons are actually double embedded solitons. We explain why these solitons do not radiate at all, even though their wavenumbers are contained in the linear spectrum of the system. Finally, we close the paper by making comments on the advantages as well as the limitations of our approach, and on further generalizations of the model and method presented.Comment: "Physical Review E, in press