Signal Propagation in Feedforward Neuronal Networks with Unreliable Synapses

In this paper, we systematically investigate both the synfire propagation and firing rate propagation in feedforward neuronal network coupled in an all-to-all fashion. In contrast to most earlier work, where only reliable synaptic connections are considered, we mainly examine the effects of unreliable synapses on both types of neural activity propagation in this work. We first study networks composed of purely excitatory neurons. Our results show that both the successful transmission probability and excitatory synaptic strength largely influence the propagation of these two types of neural activities, and better tuning of these synaptic parameters makes the considered network support stable signal propagation. It is also found that noise has significant but different impacts on these two types of propagation. The additive Gaussian white noise has the tendency to reduce the precision of the synfire activity, whereas noise with appropriate intensity can enhance the performance of firing rate propagation. Further simulations indicate that the propagation dynamics of the considered neuronal network is not simply determined by the average amount of received neurotransmitter for each neuron in a time instant, but also largely influenced by the stochastic effect of neurotransmitter release. Second, we compare our results with those obtained in corresponding feedforward neuronal networks connected with reliable synapses but in a random coupling fashion. We confirm that some differences can be observed in these two different feedforward neuronal network models. Finally, we study the signal propagation in feedforward neuronal networks consisting of both excitatory and inhibitory neurons, and demonstrate that inhibition also plays an important role in signal propagation in the considered networks.Comment: 33pages, 16 figures; Journal of Computational Neuroscience (published

Transit timing variation and activity in the WASP-10 planetary system

Transit timing analysis may be an effective method of discovering additional bodies in extrasolar systems which harbour transiting exoplanets. The deviations from the Keplerian motion, caused by mutual gravitational interactions between planets, are expected to generate transit timing variations of transiting exoplanets. In 2009 we collected 9 light curves of 8 transits of the exoplanet WASP-10b. Combining these data with published ones, we found that transit timing cannot be explained by a constant period but by a periodic variation. Simplified three-body models which reproduce the observed variations of timing residuals were identified by numerical simulations. We found that the configuration with an additional planet of mass of $\sim$0.1 $M_{\rm{J}}$ and orbital period of $\sim$5.23 d, located close to the outer 5:3 mean motion resonance, is the most likely scenario. If the second planet is a transiter, the estimated flux drop will be $\sim$0.3 per cent and can be observable with a ground-based telescope. Moreover, we present evidence that the spots on the stellar surface and rotation of the star affect the radial velocity curve giving rise to spurious eccentricity of the orbit of the first planet. We argue that the orbit of WASP-10b is essentially circular. Using the gyrochronology method, the host star was found to be $270 \pm 80$ Myr old. This young age can explain the large radius reported for WASP-10b.Comment: MNRAS accepte

Serum periostin levels in fibrous dysplasia: Its usefulness as disease biomarker. An exploratory study

Objective: Fibrous dysplasia (FD) is a rare, non-hereditary bone disease caused by a somatic mutation of GNAS gene. Periostin (Postn) is a new marker, linked to bone repair processes. We aimed to assess Postn sensitivity as disease activity marker of FD.Methods: An exploratory case-control study was led, with 15 FD patients, paired by age and gender with healthy subjects (controls). Postn serum levels were gauged in FD patients and controls, also according to clinical manifestation. In the same assay, with serum samples stored at -80°C, Postn was measured by the ELISA method (Sigma Aldrich; St. Louis, USA), [coefficient of variation (%CV) intra-assay <10% and interassay<12%]. Statistical analysis: an R Core Team 2018 processor wasused (https://www.R-project.org). A nonparametric test (MannWhitney)was used to compared Postn serum levels between the groups. ROC curves were used to find optimal cut-off points andanalyze Postn sensitivity (predictive value).Results: 15 FD patients (polyostotic 40%, monostotic 33% and McCune-Albright syndrome 27%), with an average age (X±DS) of 44.3±10 y. In our FD patient cohort, no statistically significantdifferences were observed between Postn and control group (FD: 51.1±10 ng/ml vs. control: 44.2±15 ng/ml; p=0.15) nor by FD clinical form (polyostotic: 51.8±9.1 ng/ml vs. monostotic:49.6±13 ng/ml; p=0.66). Figure 1 shows the ROC curve obtained and optimal cut-off points.Conclusion: Postn serum levels did not show statistically significant differences compared to control group or by clinical manifestation, showing low sensitivity as disease activity markerof FD.Funding: UBACYT 2018 (#0113).Fil: Mastaglia, Silvina Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: González, Diana. Mautalen Salud e Investigación ; ArgentinaFil: Tetzlaff, T. W.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; ArgentinaFil: Bonanno, Marina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Gianotti, G. R.. Mautalen Salud e Investigación ; ArgentinaFil: Fernández, F. C.. Mautalen Salud e Investigación ; ArgentinaFil: Gómez Glorioso, G. G. D.. Mautalen Salud e Investigación ; ArgentinaFil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaWorld Congress on Osteoporosis, Osteoarthritis and Musculoskeletal DiseasesBarcelonaEspañaInternational Osteoporosis FoundationEuropean Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Disease

Multi-site campaign for transit timing variations of WASP-12 b: possible detection of a long-period signal of planetary origin

The transiting planet WASP-12 b was identified as a potential target for transit timing studies because a departure from a linear ephemeris was reported in the literature. Such deviations could be caused by an additional planet in the system. We attempt to confirm the existence of claimed variations in transit timing and interpret its origin. We organised a multi-site campaign to observe transits by WASP-12 b in three observing seasons, using 0.5-2.6-metre telescopes. We obtained 61 transit light curves, many of them with sub-millimagnitude precision. The simultaneous analysis of the best-quality datasets allowed us to obtain refined system parameters, which agree with values reported in previous studies. The residuals versus a linear ephemeris reveal a possible periodic signal that may be approximated by a sinusoid with an amplitude of 0.00068+/-0.00013 d and period of 500+/-20 orbital periods of WASP-12 b. The joint analysis of timing data and published radial velocity measurements results in a two-planet model which better explains observations than single-planet scenarios. We hypothesize that WASP-12 b might be not the only planet in the system and there might be the additional 0.1 M_Jup body on a 3.6-d eccentric orbit. A dynamical analysis indicates that the proposed two-planet system is stable over long timescales.Comment: Accepted for publication in A&

Extrinsic and intrinsic determinants of nerve regeneration

After central nervous system (CNS) injury axons fail to regenerate often leading to persistent neurologic deficit although injured peripheral nervous system (PNS) axons mount a robust regenerative response that may lead to functional recovery. Some of the failures of CNS regeneration arise from the many glial-based inhibitory molecules found in the injured CNS, whereas the intrinsic regenerative potential of some CNS neurons is actively curtailed during CNS maturation and limited after injury. In this review, the molecular basis for extrinsic and intrinsic modulation of axon regeneration within the nervous system is evaluated. A more complete understanding of the factors limiting axonal regeneration will provide a rational basis, which is used to develop improved treatments for nervous system injury

Noise Suppression and Surplus Synchrony by Coincidence Detection

The functional significance of correlations between action potentials of neurons is still a matter of vivid debates. In particular it is presently unclear how much synchrony is caused by afferent synchronized events and how much is intrinsic due to the connectivity structure of cortex. The available analytical approaches based on the diffusion approximation do not allow to model spike synchrony, preventing a thorough analysis. Here we theoretically investigate to what extent common synaptic afferents and synchronized inputs each contribute to closely time-locked spiking activity of pairs of neurons. We employ direct simulation and extend earlier analytical methods based on the diffusion approximation to pulse-coupling, allowing us to introduce precisely timed correlations in the spiking activity of the synaptic afferents. We investigate the transmission of correlated synaptic input currents by pairs of integrate-and-fire model neurons, so that the same input covariance can be realized by common inputs or by spiking synchrony. We identify two distinct regimes: In the limit of low correlation linear perturbation theory accurately determines the correlation transmission coefficient, which is typically smaller than unity, but increases sensitively even for weakly synchronous inputs. In the limit of high afferent correlation, in the presence of synchrony a qualitatively new picture arises. As the non-linear neuronal response becomes dominant, the output correlation becomes higher than the total correlation in the input. This transmission coefficient larger unity is a direct consequence of non-linear neural processing in the presence of noise, elucidating how synchrony-coded signals benefit from these generic properties present in cortical networks

Estimating the contribution of assembly activity to cortical dynamics from spike and population measures

The hypothesis that cortical networks employ the coordinated activity of groups of neurons, termed assemblies, to process information is debated. Results from multiple single-unit recordings are not conclusive because of the dramatic undersampling of the system. However, the local field potential (LFP) is a mesoscopic signal reflecting synchronized network activity. This raises the question whether the LFP can be employed to overcome the problem of undersampling. In a recent study in the motor cortex of the awake behaving monkey based on the locking of coincidences to the LFP we determined a lower bound for the fraction of spike coincidences originating from assembly activation. This quantity together with the locking of single spikes leads to a lower bound for the fraction of spikes originating from any assembly activity. Here we derive a statistical method to estimate the fraction of spike synchrony caused by assemblies—not its lower bound—from the spike data alone. A joint spike and LFP surrogate data model demonstrates consistency of results and the sensitivity of the method. Combining spike and LFP signals, we obtain an estimate of the fraction of spikes resulting from assemblies in the experimental data

A Fokker-Planck formalism for diffusion with finite increments and absorbing boundaries

Gaussian white noise is frequently used to model fluctuations in physical systems. In Fokker-Planck theory, this leads to a vanishing probability density near the absorbing boundary of threshold models. Here we derive the boundary condition for the stationary density of a first-order stochastic differential equation for additive finite-grained Poisson noise and show that the response properties of threshold units are qualitatively altered. Applied to the integrate-and-fire neuron model, the response turns out to be instantaneous rather than exhibiting low-pass characteristics, highly non-linear, and asymmetric for excitation and inhibition. The novel mechanism is exhibited on the network level and is a generic property of pulse-coupled systems of threshold units.Comment: Consists of two parts: main article (3 figures) plus supplementary text (3 extra figures

Co-transplantation of Human Embryonic Stem Cell-derived Neural Progenitors and Schwann Cells in a Rat Spinal Cord Contusion Injury Model Elicits a Distinct Neurogenesis and Functional Recovery

Co-transplantation of neural progenitors (NPs) with Schwann cells (SCs) might be a way to overcome low rate of neuronal differentiation of NPs following transplantation in spinal cord injury (SCI) and the improvement of locomotor recovery. In this study, we initially generated NPs from human embryonic stem cells (hESCs) and investigated their potential for neuronal differentiation and functional recovery when co-cultured with SCs in vitro and co-transplanted in a rat acute model of contused SCI. Co-cultivation results revealed that the presence of SCs provided a consistent status for hESC-NPs and recharged their neural differentiation toward a predominantly neuronal fate. Following transplantation, a significant functional recovery was observed in all engrafted groups (NPs, SCs, NPs+SCs) relative to the vehicle and control groups. We also observed that animals receiving co-transplants established a better state as assessed with the BBB functional test. Immunohistofluorescence evaluation five weeks after transplantation showed invigorated neuronal differentiation and limited proliferation in the co-transplanted group when compared to the individual hESC-NPs grafted group. These findings have demonstrated that the co-transplantation of SCs with hESC-NPs could offer a synergistic effect, promoting neuronal differentiation and functional recovery