Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Conjunctive input processing drives feature selectivity in hippocampal CA1 neurons

Feature-selective firing allows networks to produce representations of the external and internal environments. Despite its importance, the mechanisms generating neuronal feature selectivity are incompletely understood. In many cortical microcircuits the integration of two functionally distinct inputs occurs nonlinearly through generation of active dendritic signals that drive burst firing and robust plasticity. To examine the role of this processing in feature selectivity, we recorded CA1 pyramidal neuron membrane potential and local field potential in mice running on a linear treadmill. We found that dendritic plateau potentials were produced by an interaction between properly timed input from entorhinal cortex and hippocampal CA3. These conjunctive signals positively modulated the firing of previously established place fields and rapidly induced new place field formation to produce feature selectivity in CA1 that is a function of both entorhinal cortex and CA3 input. Such selectivity could allow mixed network level representations that support context-dependent spatial maps.Howard Hughes Medical InstituteRikagaku Kenkyūjo (Japan

Measurement of the tt¯ production cross-section as a function of jet multiplicity and jet transverse momentum in 7 TeV proton-proton collisions with the ATLAS detector

The tt¯ production cross-section dependence on jet multiplicity and jet transverse momentum is reported for proton-proton collisions at a centre-of-mass energy of 7 TeV in the single-lepton channel. The data were collected with the ATLAS detector at the CERN Large Hadron Collider and comprise the full 2011 data sample corresponding to an integrated luminosity of 4.6 fb−1. Differential cross-sections are presented as a function of the jet multiplicity for up to eight jets using jet transverse momentum thresholds of 25, 40, 60, and 80 GeV, and as a function of jet transverse momentum up to the fifth jet. The results are shown after background subtraction and corrections for all known detector effects, within a kinematic range closely matched to the experimental acceptance. Several QCD-based Monte Carlo models are compared with the results. Sensitivity to the parton shower modelling is found at the higher jet multiplicities, at high transverse momentum of the leading jet and in the transverse momentum spectrum of the fifth leading jet. The MC@NLO+HERWIG MC is found to predict too few events at higher jet multiplicities

Control of excitatory synaptic strength by auxiliary subunits of AMPA receptors

The majority of excitatory synaptic transmission in the mammalian brain is mediated by the activation of AMPA-type glutamate receptors (AMPARs) by the neurotransmitter glutamate. The number of AMPARs clustered at synapses as well as their functional properties dictates the strength and timing of synaptic transmission. Therefore, determining the factors that control the trafficking and gating of AMPARs is critical to understanding how neurons process and encode information. While it was recently discovered that AMPARs interact with a family of auxiliary subunits called transmembrane AMPAR regulatory proteins (TARPs) that control the trafficking and gating of AMPARs, functional diversity among TARP family members has not been explored. In this thesis, I establish cultured cerebellar granule neurons from stargazer mutant mice as a model system to separately determine the effects of each TARP subtype on synaptic AMPAR function. I demonstrate that transfection of any of the TARP subtypes γ-2, γ-3, γ-4, or γ-8 into stargazer granule cells "rescues" the synaptic expression of native AMPARs, allowing an assessment of the vi roles of each TARP subtype in controlling synaptic AMPAR trafficking and gating (Chapters 1 and 2). I also employ TARP domain truncation and transplantation to determine which domains within TARP proteins mediate their subtype-specific effects on AMPAR trafficking and gating (Chapters 1 and 2). Finally, I exploit changes in the pharmacology of AMPARs induced by TARP binding to determine the stoichiometry of the association between TARPs and AMPARs (Chapter 3) and to infer structural information about which specific conformations of AMPARs are selectively stabilized by TARPs during gating (Chapters 4 and 5)

Regulation of AMPA receptor gating and pharmacology by TARP auxiliary subunits

Presynaptic glutamate release elicits brief waves of membrane depolarization in neurons by activating AMPA receptors. Depending on its precise size and shape, current through AMPA receptors gates downstream processes like NMDA receptor activation and action potential generation. Over a decade of research on AMPA receptor structure and function has identified binding sites on AMPA receptors for agonists, antagonists and allosteric modulators as well as key residues underlying differences in the gating behavior of various AMPA receptor subtypes. However, the recent discovery that AMPA receptors are accompanied in the synaptic membrane by a family of auxiliary subunits known as transmembrane AMPA receptor regulatory proteins (TARPs) has revealed that the kinetics and pharmacology of neuronal AMPA receptors differ in many respects from those predicted by classical studies of AMPA receptors in heterologous systems. Here, we summarize recent work and discuss remaining questions concerning the structure and function of native TARP–AMPA receptor complexes

Offline memory replay in recurrent neuronal networks emerges from constraints on online dynamics

AbstractDuring spatial exploration, neural circuits in the hippocampus store memories of sequences of sensory events encountered in the environment. When sensory information is absent during “offline” resting periods, brief neuronal population bursts can “replay” sequences of activity that resemble bouts of sensory experience. These sequences can occur in either forward or reverse order, and can even include spatial trajectories that have not been experienced, but are consistent with the topology of the environment. The neural circuit mechanisms underlying this variable and flexible sequence generation are unknown. Here we demonstrate in a recurrent spiking network model of hippocampal area CA3 that experimental constraints on network dynamics such as population sparsity, stimulus selectivity, rhythmicity, and spike rate adaptation enable additional emergent properties, including variable offline memory replay. In an online stimulus-driven state, we observed the emergence of neuronal sequences that swept from representations of past to future stimuli on the timescale of the theta rhythm. In an offline state driven only by noise, the network generated both forward and reverse neuronal sequences, and recapitulated the experimental observation that offline memory replay events tend to include salient locations like the site of a reward. These results demonstrate that biological constraints on the dynamics of recurrent neural circuits are sufficient to enable memories of sensory events stored in the strengths of synaptic connections to be flexibly read out during rest and sleep, which is thought to be important for memory consolidation and planning of future behavior.</jats:p

The Stoichiometry of AMPA Receptors and TARPs Varies by Neuronal Cell Type

SummarySynaptic AMPA receptors (AMPARs) are regulated by a family of auxiliary subunits known as transmembrane AMPA receptor regulatory proteins (TARPs). TARPs control the trafficking and gating of AMPARs. However, the number of TARP molecules that assemble within individual AMPAR channels is unknown. Here, we covalently link AMPARs to TARPs to investigate the properties of TARP/AMPAR complexes with known stoichiometry in HEK cells. We find that AMPARs are functional when associated with four, two, or no TARPs, and that the efficacy of the partial agonist kainate varies across these conditions, providing a sensitive assay for TARP/AMPAR stoichiometry. A comparison of these results with data obtained from hippocampal neurons demonstrates that native AMPARs associate with TARPs with a variable stoichiometry that depends on TARP expression level. Interestingly, AMPARs in hippocampal pyramidal neurons are saturated by TARP expression, while those in dentate gyrus granule neurons are not, indicating that variable TARP/AMPAR stoichiometry provides a mechanism for cell-type-specific regulation of AMPAR function

Recurrent Excitatory Feedback From Mossy Cells Enhances Sparsity and Pattern Separation in the Dentate Gyrus via Indirect Feedback Inhibition

It is generally appreciated that storing memories of specific events in the mammalian brain, and associating features of the environment with behavioral outcomes requires fine-tuning of the strengths of connections between neurons through synaptic plasticity. It is less understood whether the organization of neuronal circuits comprised of multiple distinct neuronal cell types provides an architectural prior that facilitates learning and memory by generating unique patterns of neuronal activity in response to different stimuli in the environment, even before plasticity and learning occur. Here we simulated a neuronal network responding to sensory stimuli, and systematically determined the effects of specific neuronal cell types and connections on three key metrics of neuronal sensory representations: sparsity, selectivity, and discriminability. We found that when the total amount of input varied considerably across stimuli, standard feedforward and feedback inhibitory circuit motifs failed to discriminate all stimuli without sacrificing sparsity or selectivity. Interestingly, networks that included dedicated excitatory feedback interneurons based on the mossy cells of the hippocampal dentate gyrus exhibited improved pattern separation, a result that depended on the indirect recruitment of feedback inhibition. These results elucidate the roles of cellular diversity and neural circuit architecture on generating neuronal representations with properties advantageous for memory storage and recall.</jats:p