A calcium-based plasticity model for predicting long-term potentiation and depression in the neocortex

Pyramidal cells (PCs) form the backbone of the layered structure of the neocortex, and plasticity of their synapses is thought to underlie learning in the brain. However, such long-term synaptic changes have been experimentally characterized between only a few types of PCs, posing a significant barrier for studying neocortical learning mechanisms. Here we introduce a model of synaptic plasticity based on data-constrained postsynaptic calcium dynamics, and show in a neocortical microcircuit model that a single parameter set is sufficient to unify the available experimental findings on long-term potentiation (LTP) and long-term depression (LTD) of PC connections. In particular, we find that the diverse plasticity outcomes across the different PC types can be explained by cell-type-specific synaptic physiology, cell morphology and innervation patterns, without requiring type-specific plasticity. Generalizing the model to in vivo extracellular calcium concentrations, we predict qualitatively different plasticity dynamics from those observed in vitro. This work provides a first comprehensive null model for LTP/LTD between neocortical PC types in vivo, and an open framework for further developing models of cortical synaptic plasticity.We thank Michael Hines for helping with synapse model implementation in NEURON; Mariana Vargas-Caballero for sharing NMDAR data; Veronica Egger for sharing in vitro data and for clarifications on the analysis methods; Jesper Sjöström for sharing in vitro data, helpful discussions, and feedback on the manuscript; Ralf Schneggenburger for helpful discussions and clarifications on the NMDAR calcium current model; Fabien Delalondre for helpful discussions; Francesco Casalegno and Taylor Newton for helpful discussion on model fitting; Daniel Keller for helpful discussions on the biophysics of synaptic plasticity; Natali Barros-Zulaica for helpful discussions on MVR modeling and generalization; Srikanth Ramaswamy, Michael Reimann and Max Nolte for feedback on the manuscript; Wulfram Gerstner and Guillaume Bellec for helpful discussions on synaptic plasticity modeling. This study was supported by funding to the Blue Brain Project, a research center of the École polytechnique fédérale de Lausanne, from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology. E.B.M. received additional support from the CHU Sainte-Justine Research Center (CHUSJRC), the Institute for Data Valorization (IVADO), Fonds de Recherche du Québec–Santé (FRQS), the Canada CIFAR AI Chairs Program, the Quebec Institute for Artificial Intelligence (Mila), and Google. R.B.P. and J.DF. received support from the Spanish “Ministerio de Ciencia e Innovación” (grant PGC2018-094307-B-I00). M.D. and I.S. were supported by a grant from the ETH domain for the Blue Brain Project, the Gatsby Charitable Foundation, and the Drahi Family Foundation

Hadronization effects in event shape moments

We study the moments of hadronic event shapes in $e^+e^-$ annihilation within the context of next-to-next-to-leading order (NNLO) perturbative QCD predictions combined with non-perturbative power corrections in the dispersive model. This model is extended to match upon the NNLO perturbative prediction. The resulting theoretical expression has been compared to experimental data from JADE and OPAL, and a new value for $\alpha_s(M_Z)$ has been determined, as well as of the average coupling $\alpha_0$ in the non-perturbative region below $\mu_I=2$ GeV within the dispersive model: \alpha_s(M_Z)&=0.1153\pm0.0017(\mathrm{exp})\pm0.0023(\mathrm{th}),\alpha_0&=0.5132\pm0.0115(\mathrm{exp})\pm0.0381(\mathrm{th}), The precision of the $\alpha_s(M_Z)$ value has been improved in comparison to the previously available next-to-leading order analysis. We observe that the resulting power corrections are considerably larger than those estimated from hadronization models in multi-purpose event generator programs.Comment: 23 pages, 5 figures, 15 tables. Few minor changes. Version accepted for publication in European Physical Journal C

The SM and NLO multileg working group: Summary report

This report summarizes the activities of the SM and NLO Multileg Working Group of the Workshop "Physics at TeV Colliders", Les Houches, France 8-26 June, 2009.Comment: 169 pages, Report of the SM and NLO Multileg Working Group for the Workshop "Physics at TeV Colliders", Les Houches, France 8-26 June, 200

Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study : changes in treatment uptake and outcomes between 1991 and 2013

Background: The hepatitis C virus (HCV) epidemic is evolving rapidly in patients infected with human immunodeficiency virus (HIV). We aimed to describe changes in treatment uptake and outcomes of incident HCV infections before and after 2006, the time-point at which major changes in HCV epidemic became apparent. Methods.  We included all adults with an incident HCV infection before June 2012 in the Swiss HIV Cohort Study, a prospective nationwide representative cohort of individuals infected with HIV. We assessed the following outcomes by time period: the proportion of patients starting an HCV therapy, the proportion of treated patients achieving a sustained virological response (SVR), and the proportion of patients with persistent HCV infection during follow-up. Results.  Of 193 patients with an HCV seroconversion, 106 were diagnosed before and 87 after January 2006. The proportion of men who have sex with men increased from 24% before to 85% after 2006 (P < .001). Hepatitis C virus treatment uptake increased from 33% before 2006 to 77% after 2006 (P < .001). Treatment was started during early infection in 22% of patients before and 91% after 2006 (P < .001). An SVR was achieved in 78% and 29% (P = .01) of patients treated during early and chronic HCV infection. The probability of having a detectable viral load 5 years after diagnosis was 0.67 (95% confidence interval [CI], 0.58-0.77) in the group diagnosed before 2006 and 0.24 (95% CI, 0.16-0.35) in the other group (P < .001). Conclusions. In recent years, increased uptake and earlier initiation of HCV therapy among patients with incident infections significantly reduced the proportion of patients with replicating HCV

Aquatic Habits and Niche Partitioning in the Extraordinarily Long-Necked Triassic Reptile Tanystropheus

Tanystropheus longobardicus is one of the most remarkable and iconic Triassic reptiles. Mainly known from the Middle Triassic conservation Lagerstätte of Monte San Giorgio on the Swiss-Italian border, it is characterized by an extraordinarily long and stiffened neck that is almost three times the length of the trunk, despite being composed of only 13 hyper-elongate cervical vertebrae [1-8]. Its paleobiology remains contentious, with both aquatic and terrestrial lifestyles having been proposed [1, 9-12]. Among the Tanystropheus specimens, a small morphotype bearing tricuspid teeth and a large morphotype bearing single-cusped teeth can be recognized, historically considered as juveniles and adults of the same species [4]. Using high-resolution synchrotron radiation microtomography (SRμCT), we three-dimensionally reconstruct a virtually complete but disarticulated skull of the large morphotype, including its endocast and inner ear, to reveal its morphology for the first time. The skull is specialized toward hunting in an aquatic environment, indicated by the placement of the nares on the top of the snout and a "fish-trap"-type dentition. The SRμCT data and limb bone paleohistology reveal that the large morphotype represents a separate species (Tanystropheus hydroides sp. nov.). Skeletochronology of the small morphotype specimens indicates that they are skeletally mature despite their small size, thus representing adult individuals of Tanystropheus longobardicus. The co-occurrence of these two species of disparate size ranges and dentitions provides strong evidence for niche partitioning, highlighting the surprising versatility of the Tanystropheus bauplan and the complexity of Middle Triassic nearshore ecosystems.© 2020 Elsevier Inc. The attached document is the author(’s’) final accepted/submitted version of the journal article. You are advised to consult the publisher’s version if you wish to cite from it

Osteology of a New Specimen of Macrocnemus aff. M. fuyuanensis (Archosauromorpha, Protorosauria) from the Middle Triassic of Europe: Potential Implications for Species Recognition and Paleogeography of Tanystropheid Protorosaurs

Over the past two decades, a wealth of marine and terrestrial reptiles, including protorosaurian archosauromorphs, has been described from Triassic shales and limestone layers in southern China. Recovered from the eastern margin of the Tethys Ocean, these forms often show remarkable similarities to taxa that were previously known and described from Europe, i.e., the western Tethyan margin. One protorosaurian that is known from the western and the eastern Tethyan province is the genus Macrocnemus, with currently three recognized species: (1) Macrocnemus bassanii from the Middle Triassic Besano Formation and Meride Limestone (late Anisian–early Ladinian), UNESCO World Heritage Site Monte San Giorgio, Ticino, Switzerland; (2) Macrocnemus obristi from the Prosanto Formation (early Ladinian) of the Ducan area, Grisons, Switzerland; and (3) Macrocnemus fuyuanensis from the Falang Formation (Ladinian), Yunnan Province, southern China. Recently a new specimen, PIMUZ T 1559, from the upper Besano Formation at Meride, Ticino, Switzerland, was prepared, revealing a disarticulated skeleton which includes most of the cranium and lower jaw, pre-caudal vertebral column and ribs, the forelimbs, and girdle elements. Unambiguously assignable to the genus Macrocnemus, it evinces particularly gracile elongated cervical ribs, as well as a humerus/radius ratio that is comparable only to that of M. fuyuanensis from southern China. Based on this feature we tentatively recognize the new specimen as M. aff. fuyuanensis from Europe. The position and exquisite preservation of the clavicle and interclavicle in this specimen allows a revision of the shoulder girdle of Macrocnemus when articulated, which also has implications for closely related protorosaurian taxa, such as the long-necked Tanystropheus. Furthermore, differences in the shape and morphology of the interclavicle including pointed wing-like lateral processes and a short, fusiform caudal process represent rare discrete characters that allow separation of the specimens of M. bassanii from the new specimen of M. aff. fuyuanensis